Dialysis system having disposable cassette and interface therefore

ABSTRACT

A medical fluid flow control system includes an interface including a first pump area, the first pump area of the interface including a pneumatic actuator port and a gasket seal port; and a membrane gasket including a second pump area for mating with the first pump area, the second pump area including a blind section which covers the pneumatic actuator port when the gasket is mated with the interface, the second pump area further including an aperture, the aperture sized and positioned to seal around the gasket seal port, allowing a negative pressure to be applied through the gasket seal port to a flexible sheet of a pumping cassette.

BACKGROUND

The examples discussed below relate generally to medical fluid delivery.More particularly, the examples disclose systems, methods andapparatuses for automated peritoneal dialysis (“APD”).

Due to various causes, a person's renal system can fail. Renal failureproduces several physiological derangements. The balance of water,minerals and the excretion of daily metabolic load is no longer possibleand toxic end products of nitrogen metabolism (urea, creatinine, uricacid, and others) can accumulate in blood and tissue.

Kidney failure and reduced kidney function have been treated withdialysis. Dialysis removes waste, toxins and excess water from the bodythat normal functioning kidneys would otherwise remove. Dialysistreatment for replacement of kidney functions is critical to many peoplebecause the treatment is life saving.

One type of kidney failure therapy is peritoneal dialysis, which infusesa dialysis solution, also called dialysate, into a patient's peritonealcavity via a catheter. The dialysate contacts the peritoneal membrane ofthe peritoneal cavity. Waste, toxins and excess water pass from thepatient's bloodstream, through the peritoneal membrane and into thedialysate due to diffusion and osmosis, i.e., an osmotic gradient occursacross the membrane. The spent dialysate is drained from the patient,removing waste, toxins and excess water from the patient. This cycle isrepeated.

There are various types of peritoneal dialysis therapies, includingcontinuous ambulatory peritoneal dialysis (“CAPD”), automated peritonealdialysis (“APD”), tidal flow dialysate and continuous flow peritonealdialysis (“CFPD”). CAPD is a manual dialysis treatment. Here, thepatient manually connects an implanted catheter to a drain, allowingspent dialysate fluid to drain from the peritoneal cavity. The patientthen connects the catheter to a bag of fresh dialysate, infusing freshdialysate through the catheter and into the patient. The patientdisconnects the catheter from the fresh dialysate bag and allows thedialysate to dwell within the peritoneal cavity, wherein the transfer ofwaste, toxins and excess water takes place. After a dwell period, thepatient repeats the manual dialysis procedure, for example, four timesper day, each treatment lasting about an hour. Manual peritonealdialysis requires a significant amount of time and effort from thepatient, leaving ample room for improvement.

Automated peritoneal dialysis (“APD”) is similar to CAPD in that thedialysis treatment includes drain, fill, and dwell cycles. APD machines,however, perform the cycles automatically, typically while the patientsleeps. APD machines free patients from having to manually perform thetreatment cycles and from having to transport supplies during the day.APD machines connect fluidly to an implanted catheter, to a source orbag of fresh dialysate and to a fluid drain. APD machines pump freshdialysate from a dialysate source, through the catheter, into thepatient's peritoneal cavity, and allow for the dialysate to dwell withinthe cavity and for the transfer of waste, toxins and excess water totake place. The source can be multiple sterile dialysate solution bags.

APD machines pump spent dialysate from the peritoneal cavity, though thecatheter, to the drain. As with the manual process, several drain, filland dwell cycles occur during dialysis. A “last fill” occurs at the endof APD, which remains in the peritoneal cavity of the patient until thenext treatment.

Both CAPD and APD are batch type systems that send spent dialysis fluidto a drain. Tidal flow systems are modified batch systems. With tidalflow, instead of removing all of the fluid from the patient over alonger period of time, a portion of the fluid is removed and replacedafter smaller increments of time.

Some continuous flow, or CFPD, systems clean or regenerate spentdialysate instead of discarding it. Others use a large volume of freshdialysate. The systems pump fluid into and out of the patient, through aloop. In a regenerating system, dialysate flows into the peritonealcavity through one catheter lumen and out another catheter lumen. Thefluid exiting the patient passes through a reconstitution device thatremoves waste from the dialysate, e.g., via a urea removal column thatemploys urease to enzymatically convert urea into ammonia. The ammoniais then removed from the dialysate by adsorption prior to reintroducingthe dialysate into the peritoneal cavity. Additional sensors areemployed to monitor the removal of ammonia. Regenerating CFPD systemsare typically more complicated than batch systems.

PD systems, home hemodialysis/hemofiltration, and intensive care unitprocedures that use bagged peritoneal or hemodialysis dialysate,hemofiltration substitution solution can use a dual chamber bag. Forexample, bicarbonate based solutions have been developed for certainones of the above applications. Bicarbonate is unstable in the presenceof magnesium and calcium and forms a precipitate after a period of time.The bicarbonate based solutions are accordingly provided in a dualchamber bag. Prior to use a seal between the two chambers is broken andthe two concentrate solutions are mixed and used before calcium ormagnesium precipitate can form. Unfortunately, a single concentratesolution delivered to a patient due to the two concentrate solutions notmixing can create a physiologically unsafe condition for the patient.

The system below addresses various drawbacks with the above-mentionedmedical fluid treatments.

SUMMARY

The present disclosure describes an improved automated peritonealdialysis (“APD”) system, however, many of the teachings herein areapplicable to other medical fluid treatments, especially other renalfailure therapy treatments, such as hemodialysis (“HD”), hemofiltration(“HF”), hemodiafiltration (“HDF”) and continuous renal replacementtherapy (“CRRT”).

The system offers improved treatment and ease of use features. Thesystem is mobile in one embodiment so that the patient can, for example,start a therapy in the family room and move the system to a bedroom onthe same floor. The system manages supply bags, which are carried withthe device or instrument when the patient moves the instrument. Thesystem also employs a bag management system, which tilts the supply bagsso that gravity will cause fluid to flow from them, leaving air behindduring the priming sequence and normal operation. The gravity inducedair separation at the supply bags allows the system to pump at highflowrates because there is little concern that the air has not beenremoved properly while pumping the fluid.

The system provides a cart having a rotating bearing plate or “lazySusan” that supports the instrument and allows it to be rotated forconvenient operation, making at least the vast majority of systemfeatures readily accessible. This may allow the patient to correct mostalarms without getting out of bed. The “lazy Susan” plate can optionallyhave detent positions every ninety degrees or so.

The system includes an improved priming procedure using a patient linehaving dual lumens. During the patient line prime, fluid flows down onelumen away from a disposable cassette and back up the other lumentowards the cassette forming a closed loop feedback that indicates whenpriming is complete. This feedback is operable even with patient lineextensions. U.S. Patent Application No. 2004/0019312 A1, FIG. 2, ownedby the eventual assignee of the present disclosure, shows a tipprotector for a dual lumen patient line that is compatible with thispriming technique. The dual lumen line also eliminates the volume ofspent effluent fluid that is pushed back (recirculated) when theinstrument cycles from drain to fill. Additionally, the dual lumen lineaccommodates the sensing of intraperitoneal pressure (“IPP”) to optimizepatient fill and drain volumes as described in U.S. Pat. No. 6,497,676,owned by the eventual assignee of the present disclosure, the entirecontents of which are incorporated expressly herein by reference.Further still, the dual lumen patient line allows the same disposableset to be used for large and small patients because the recirculationvolume is near zero.

The system also provides an auto-connection mechanism that connectsconnectors from the supply bags to connectors of the cassette supplylines. In one embodiment, the system provides for up to four supplybags, which can be connected to a manifold of the auto-connectionmechanism. Each solution bag can be the same or different. Theauto-connection mechanism is advantageously able to use the samesolution bag (e.g., made having existing spikes and spike septums withexisting equipment and processes). Tip protectors which protect thesupply and bag pigtail connectors are modified to be compatible with theauto-connection mechanism.

As discussed in detail below, the system of the present disclosure isreadily adapted for a high-volume therapy. In one implementation, thesystem uses four-to-one manifolds, which allow any one or more of foursupply bag inlets to the disposable cassette be increased to up to fourbags for treatment. The four-to-one manifolds work in conjunction withthe auto-connection and auto-identification systems described herein. Upto four, four-to-one manifolds each being able to connect to up to four,e.g., same-solution, supply bags can accommodate a therapy volume of,for example, up to ninety-six liters.

Each of the manifold lines in the four-to-one manifold is placed in theauto-connection mechanism for connection to the supply lines connectedto the disposable cassette. The single supply line of the disposablecassette can now connect to up to four solution bags. An imaging systemrecognizes the four to one connector and the type of attachment made tothe manifold (the one line) end of the four to one manifold.

The auto-connection system also includes an automatic clamping system,which allows the user to not have to clamp and unclamp solution linesduring the connection process or when an alarm condition occurs.

The imaging system or solution identification system which verifies thevolume, expiration date, composition, and configuration (e.g., singlebag solution, multiple chamber bag solution, or multiple bag solutionthat requires mixing) before the bags are connected. The solutionidentification system verifies that the composition and volume of thesolutions are consistent with the therapy prescription beforeconnection. The solution identification system also: (i) automaticallydraws solution in the correct sequence when the correct solution bagsare loaded; (ii) informs the user if the incorrect solution bags areloaded; and (iii) alerts the user if a solution bag connector isdeformed, potentially causing an improper connection.

The disposable set (cassette, bags and lines) of the system isrelatively simple and easy to use and requires fewer product codesbecause all geographic regions can use the same disposable set for bothpediatric patients and adult patients, and with therapy volumes up toninety-six liters. The lines of the disposable set are connected toorganizers (e.g., cassette supply lines connected to a first organizerand patient and drain lines connected to a second organizer), whichprevent the lines from becoming tangled and facilitates loading thelines into the auto-connection system.

The disposable set allows for admixing as described in U.S. Pat. No.5,925,011, owned by the eventual assignee of the present disclosure, theentire contents of which are incorporated expressly herein by reference,or for the delivery of single part solutions, or double part solutionscontained in a single bag. If a peel seal or frangible needs to bebroken before use, the system can verify that it has been broken beforethe solution is delivered to the patient. Capacitive sensors located onthe bag management shelves are used to verify that the seal has beenbroken and that the same solution is present in both chambers (ends) ofthe solution bag.

In an alternative embodiment, the sensor is an inductive sensor, whichcan (i) detect whether a emitter chamber bag has been loaded properlyonto one of the bag management shelves and (ii) detect whether afrangible seal between two chambers bags has been broken such that theconcentrate solutions can mixed properly for delivery to the patient.The inductive sensing apparatus and method are not limited to renalapplications and can be used confirm placement, mixing, etc., for anymedical fluid system using dual or multi-chamber bagged solutions.

The system further provides a non-invasive temperature measuring featureor technique. The heat sensing technique uses a non-invasive infraredtemperature sensor and electromagnet. The electromagnet controls theorientation of the temperature sensor. The disposable cassette hassheeting with a black or opaque area. A first orientation of theinfrared sensor is trained on the black or opaque area and consequentlymeasures the temperature of the sheeting. The second orientation of theinfrared sensor is trained on an area of the sheeting which is not blackor opaque and can thus see through the sheeting into the fluid behindthe sheeting. This second infrared sensor reading measures a combinationof the temperature of the film and the fluid. Discussed herein arealgorithms for calculating the temperature of the fluid from the twoinfrared temperature readings.

The HomeChoice® APD System marketed by the eventual assignee of thepresent disclosure, uses a method described in U.S. Pat. No. 4,826,482(“The '482 Patent”), to determine the volume of fluid pumped to thepatient or to the drain. That method in essence looks backwards after apump stroke to see how much fluid has been pumped to the patient. Whilethis system has been highly successful, there are various reasons toknow the volume of fluid pumped during the pump stroke or in real time.The reasons are discussed in detail below but in general include: (i)being able to fill/drain a patient to a volume that is not equal to awhole number of pump strokes; (ii) being able to immediately know when apatient is drained to empty or virtually empty to reduce pain at the endof drain; (iv) providing accuracy needed for mixing solutions; and (v)helping to eliminate the need to have to provide an alternate source offluid, so that a partially full pump chamber can be differentiated froma pump chamber containing air and fluid.

The real time system and method in one embodiment monitors the pressuredecay in a pressurized tank in fluid communication with the pump chamberof the disposable cassette. The system knows the volume of air or gas(V_(gas)) in the pump chamber prior to opening the valve to the tank.Then, after the valve to the tank is opened the system takes pressurereadings at desired intervals and performs a calculation after eachreading. The initial pressure (P1) in the tank is known. If the pressureat any given point in time is taken as P1′ then a ratio can be expressedin an equation form as follows:

(P1/P1′−1),

this ratio is multiplied by an addition of the gas volume V_(gas) to aknown volume of the tank V_(tank) to form a real time volume of fluidpumped V_(fluid)=(P1/P1′−1)(V_(tank)+V_(gas)). P1 is initially equal toP1′, thus making the initial real time volume of fluid pumped equal tozero. As P1′ becomes increasingly less than P1 over time, (P1/P1′−1)becomes increasingly larger over time as does V_(fluid).

The real time volumes are useful for many purposes as described above.Described below is an algorithm for using the real time volumes todetermine features such as: (i) if a full pump stroke has occurred; (ii)if a line occlusion has occurred; (iii) if a leak has occurred; and (iv)if multiple concentrates have been mixed properly, for example.

The cassette in one embodiment has sheeting welded to the molded plasticpiece as described in U.S. Pat. Nos. 5,401,342, 5,540,808, 5,782,575 and6,001,201. In an alternative embodiment, the molded plastic piece isenclosed within welded sheeting but not welded to the sheeting. Thesheeting in one embodiment is welded to itself and to the tubingattached to the cassette, allowing the inside of the sheeting includingthe molded plastic piece to be isolated from the environment. Thiscassette assembly provides flexibility in material selection for themolded plastic, sheeting and tubing because the sheeting to moldedplastic seal has been eliminated. The sheeting material therefore doesnot need to be compatible with the rigid cassette material from awelding or bonding standpoint.

A disposable cassette having three pumping chambers is also shown anddescribed below. The three chamber cassette provides a number ofadvantages, such as allowing for continuous flow at both the inlet andoutlet of the pump even when running a standard, e.g., batch, therapy.With two pump chambers, fluid measurement is performed in an attempt tomake patient flow essentially continuous. For example, the fluidmeasurements can be made in one pump chamber, while the other pumpchamber is halfway through its pump stroke and vice versa. Nevertheless,the fresh supply and drain flowrates are pulsatile because more fluidwill be flowing at certain times than at others. The three pump cassettealso allows for continuous flow to a patient even when two solutions arebeing mixed online.

The system also includes an improved cassette/manifold membrane assemblyor system. The assembly or system includes a interface plate having pumpactuation areas with actuation ports for allowing a positive or negativepressure to be applied within the pump actuation areas to the membranegasket to correspondingly place a positive or negative pressure on ajuxtaposed flexible sheeting of the disposable cassette. Likewise, theinterface plate includes valve actuation areas with actuation ports forallowing a positive or negative pressure to be applied within the valveactuation areas to the membrane gasket to correspondingly place apositive or negative pressure on the juxtaposed flexible sheeting of thedisposable cassette. In addition to the actuation ports, the cassetteinterface includes an evacuation port to evacuate air between themembrane gasket and cassette sheeting adjacent to each pump and eachvalve.

The gasket includes blind holes that seal around the sidewalls of theactuation ports of the valves or pump chambers. The blind holes includea sheath or thin portion that extends over the valve or pump actuationports. Positive or negative pressure applied through actuation ports istherefore likewise applied to the sheath portion of the blind hole ofthe members. Positive or negative pressure applied to the sheath portionaccordingly causes a flexing of the sheath portion and correspondingflexing of the cassette sheeting.

The membrane also provides a through-hole for each evacuation port ofthe interface plate. The through-holes seal around the sidewalls of theprotruding evacuation ports and allow a negative pressure appliedthrough the evacuation ports to suck the cassette sheeting against thesheath portions of the membrane gasket forming pump or valve areas. Inthis manner, for a given pump or valve area, the membrane gasket andcassette sheeting flex back and forth together.

If a hole develops in either the membrane gasket or the cassettesheeting, the vacuum level through the evacuation port at the leakdecreases, indicating the leak. Thus the evacuation ports also serve asleak detectors that are placed in multiple places over the cassette,providing superior leak detection with the capability of indicatingwhere on the cassette sheeting or membrane gasket the leak has occurred.This leak detection capability is present prior to the beginning oftherapy as well as during therapy.

The system can also tell which of the membrane gasket and the cassettesheeting has incurred a leak. If fluid is not drawn between the membranegasket and the sheeting, the leak is in the membrane gasket. If fluid isdrawn into between the membrane gasket and the sheeting, the leak is inthe cassette sheeting. This can be a valuable tool, for example, indiagnosing a machine that appears to be malfunctioning.

The cassette interface, in an embodiment, also integrates the pneumaticmanifold with the cassette interface so that air that travels from theback side of the pumping chambers of the disposable cassette to thevolumetric reference chambers (one for each pump chamber, used forvolumetric accuracy calculation and air) of the pneumatic manifold doesnot have to travel far. The close spacing also tends to make thetemperature of air in the passageways, the reference chambers and thepump chambers equal. This is useful for a pneumatic pumping techniquethat assumes a constant temperature between air in the volumetricreference chambers and the medical fluid or dialysate pumped though thedisposable cassette. The dialysate is located on the other side of thecassette sheeting from air in communication with the pneumatic sourceand the volumetric reference chamber. The fluid temperature needs to beabout that of the human body, e.g., about 37° C. The air in thereference chamber therefore should be about 37° C.

The system in one embodiment provides a heater at the cassetteinterface, which heats the interface plate, the volumetric referencechambers and the pneumatic passageways to a single temperature tostabilize the entire pneumatic circuit at a desired temperature. Theheated interface plate also enables the reference chambers to be broughtto temperature more quickly, especially on cold days. A quick warm-upalso saves a substantial amount of time during the calibration of thesystem. The interface plate in one embodiment is made entirely of metal,which can be heated. Alternatively, a cassette interface portion of themanifold, to which pneumatic control valves controlling pressure to thefluid valves are attached, is plastic. The reference chambers are metaland are provided in a module with a heating element, such as a resistiveheating element. The module is affixed to the plastic interface. Theinterface includes pump chamber walls having a metal or thermallyconductive section. Heat is thereby transferred to the pump chamberinterface wall, which heats air therein.

It is therefore an advantage of the present disclosure to provide animproved medical fluid system, such as for APD, HD, HF, HDF and CRRT.

It is another advantage of the present disclosure to provide a medicalfluid system having a rotatable base, making device features readilyaccessible.

Moreover, it is an advantage of the present disclosure to provide amedical fluid system that is relatively mobile and that carries thesupply bags as the system is moved.

It is a further advantage of the present disclosure to provide a medicalfluid system that positions fluid supply bags so as to tend to trap airin the bags.

Another advantage of the present disclosure is to provide a non-invasivetemperature sensing apparatus and method.

It is yet a further advantage of the present disclosure to provide adisposable cassette wherein at least one of: (i) the cassette includesthree pumping chambers; and (ii) the molded plastic part of the cassetteis provided inside a pouch made of flexible sheeting sealed together andto tubing attached to the molded plastic part.

It is still another advantage of the present disclosure to provide amethod and apparatus for real time measurement of fluid volume pumped.

Further still, it is an advantage of the present disclosure to provide afluid management system (“FMS”), which has improved temperature controlfor a fluid volume measuring system using the ideal gas law.

Yet another advantage of the present disclosure is to provide forimproved leak detection in a pneumatically actuated pumping system.

Still further, it is an advantage of the present disclosure to providean improved cassette/manifold membrane gasket.

Yet a further advantage of the present disclosure is to provide anauto-connection mechanism for solution lines and an auto-identificationmechanism to ensure that a proper solution at a proper volume for aparticular supply bag will be delivered to a patient.

Still a further advantage of the present disclosure is provide animproved priming technique using a dual lumen patient line and anapparatus and method for automatically connecting the dual lumen patientline to a dual port transfer set.

Further still, an advantage of the present disclosure is to provide anapparatus and method for automatically detecting whether a solution baghas been loaded for therapy.

A related advantage is to use the above bag detection apparatus andmethod for automatically detecting whether a multi-chamber solution baghas been opened properly so that the solution inside is mixed properlyfor delivery to the patient.

A further related advantage is that the above bag detection apparatusand method is non-invasive, maintaining the sterility of theconcentrates and preserving the bag and other solution disposables.

Additional features and advantages are described herein, and will beapparent from, the following Detailed Description and the figures.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates one embodiment of a dialysis system cart with amachine holding, rotatable bearing.

FIG. 2 illustrates the cart of FIG. 1, in which the dialysis machine hasbeen rotated to have the solution bags facing a front of the cart.

FIG. 3 illustrates a system using the cart of FIG. 1, in which thedialysis machine has been rotated to have machine controls facing afront of the cart.

FIGS. 4 to 9 illustrate one embodiment for a supply bag loadingprocedure for a bag management system of a dialysis system of thepresent disclosure.

FIG. 10 is a perspective view of one embodiment of a disposable set ofthe system of the present disclosure.

FIG. 11 is a perspective view of one embodiment of a four-to onemanifold useable with the disposable set of FIG. 10.

FIG. 12 is a perspective view of one embodiment of an instrument of thesystem of the present disclosure, which includes an auto-connectionmechanism operable with the disposable set of FIG. 10.

FIGS. 13A to 13I are perspective views illustrating one embodiment of asupply line auto-connection sequence using the auto-connection mechanismof FIG. 12.

FIG. 14 is a perspective view of one embodiment of anauto-identification mechanism operable with the auto-connectionmechanism of FIG. 12.

FIGS. 15A to 15E illustrate one embodiment of a patient lineauto-connection sequence using the auto-connection mechanism of FIG. 12.

FIG. 16 is a perspective view of one embodiment for a disposable pumpingcassette having a rigid portion held in a sealed pump sheeting pouch.

FIGS. 17A and 17B are front and rear views, respectively, of oneembodiment of a disposable pumping cassette having three pump chambers.

FIG. 17C shows one possible valve arrangement for the three pump chambercassette of FIGS. 17A and 17B for achieving the pumping regimes shown inconnection with FIGS. 18A to 18C.

FIGS. 18A to 18C are schematic views showing pumping sequences using thethree pump chamber cassette of FIGS. 17A and 17B.

FIG. 19 is a perspective view of one embodiment of a pneumatic pumpingsystem of the present disclosure, which includes a manifold cassetteinterface, a membrane gasket and a disposable cassette.

FIG. 20 is a perspective view of a manifold cassette interface andmembrane gasket of the pneumatic pumping system of FIG. 19.

FIG. 21 is a perspective view of an interface plate of the cassetteinterface of the pneumatic pumping system of FIG. 19.

FIG. 22 is a perspective view of a membrane gasket of the pneumaticpumping system of FIG. 19.

FIG. 23 is a perspective view of the reverse side of the interface plateof FIG. 21, which is metallic and can include a heating strip forheating the reference chambers formed in the interface plate.

FIG. 24 is a perspective view of a reverse side of an alternativemanifold, which includes a plastic interface and control valveconnection portion and a heated reference chamber module connected tothe plastic portion.

FIGS. 25A and 25B are front and rear perspective views of the plasticinterface and control valve connection portion of the assembly of FIG.24.

FIGS. 26A and 26B are front and rear perspective views of the heatedreference chamber module of the assembly of FIG. 24.

FIG. 27 is a schematic view of an embodiment of a pneumatic system foroperating a real time method for determining volume of fluid moved.

FIGS. 28A to 28F illustrate one embodiment of a real time method fordetermining volume of fluid moved.

FIG. 29 is a chart of real time fluid volumes calculated via the methodof FIGS. 28A to 28F.

FIG. 30 is a schematic flow chart illustrating an example ofpneumatically actuated pumps undergoing a fill with fresh fluid phase,using the real time method discussed in connection with FIGS. 28A to28F, and wherein the dialysis system employs inline mixing of dextroseand bicarbonate concentrates.

FIG. 31 is a schematic flow chart illustrating an example of thepneumatically actuated pumps undergoing a fill with effluent (drainingfluid from the patient) phase, using the real time method discussed inconnection with FIGS. 28A to 28F.

FIG. 32 is a schematic view of one embodiment for a non-invasivetemperature sensing system and method having a temperature sensor in afirst position.

FIG. 33 is a schematic view of one embodiment for a non-invasivetemperature sensing system and method having a temperature sensor in asecond position.

FIG. 34 is a graph comparing the results of the temperature sensingsystem of FIGS. 32 and 33 versus those of an invasive temperaturesensor.

FIG. 35 is a schematic illustration of one embodiment of an inductivesolution container loading system in a “not mixed” sensing state.

FIG. 36 is a schematic illustration of the system embodiment of FIG. 35in a “mixed” sensing state.

FIGS. 37A to 37D are schematic views of one embodiment of an inductivesensing system employing multiple emitters and receiving the systemcapable of orientation detector supply container loading.

DETAILED DESCRIPTION Mobile Cart System

Referring now to the drawings and in particular to FIGS. 1 to 3, adialysis system, such as an automated peritoneal dialysis (“APD”) system10 is illustrated. It should be appreciated that system 10 can be usedwith other types of renal failure therapy systems, such as any of thosemaintained above.

FIG. 1 illustrates that system 10 includes a mobile cart 12, whichallows the system to be moved readily, e.g., from a family room to abedroom and vice versa. Cart 12 includes a lazy Susan-type bearing 14,which provides ample access to the controls 22 and bag management system30 of instrument 20 at all times. Bag management system 30 organizes theloading of supply bags at the beginning of therapy as shown in detailherein. Lazy Susan bearing 14 in one embodiment is equipped with detentsthat prevent the system from rotating during operation. A cut-out orhole in the center of lazy Susan bearing 14 allows a power cord to passthrough to shelves 16 of cart 12. Lazy Susan bearing 14 can also have atotal rotation limit, e.g., 360 degrees or so, to prevent damage to thepower cord due to over-rotation.

Instrument 20 can, for example, be rotated to face the patient toprovide ready access to the bag management shelves of bag managementsystem 30. Instrument 20 can then be rotated to provide optimum accessto the controls 22, display 24, auto-connection mechanism 26 andcassette loading mechanism 28 during the set-up procedure as seen inFIG. 3. Also, instrument 20 can be rotated so that the display 24 andcontrols 22 face the patient's bed when the patient is asleep. Here, ifan alarm sounds, the patient can potentially access controls 22, drainline, supply bags lines, etc., without getting out of bed.

Mobile cart 12 includes shelves or drawers 16, which hold the ancillarysupplies needed for a dialysis therapy. To move system 10, the patientneeds to unplug a power cord. Mobile cart 12 accommodates the drain bag,e.g., on lower shelf 16. The self-contained drain cart allows cart 12 tobe moved without having to first load the drain bag. If a drain line isrun to a house drain instead of a bag, the drain line likely has to beremoved from the drain and placed onto cart 12 when system 10 is moved.A handle 18 facilitates moving system 10 and in one embodiment can berotated upwardly for movement of cart 12 and downwardly and out of theway when not needed.

Bag Management System

Referring now to FIGS. 4 to 9, an embodiment for bag management system30 of dialysis system 10 is illustrated. As illustrated, bag managementsystem 30 is connected to or made integral with instrument or cycler 20.Bag management system 30 as illustrated is configured for four, e.g.,six liter supply bags 40 a to 40 d (referred to herein collectively assupply bags 40 or generally, individually as supply bag 40). System 30is configured alternatively to hold more or less six liter bags 40.FIGS. 4 to 9 also show that cycler 20 includes a hinged display 24,which can operate with separate controls 22 and/or a touch screenoverlay.

FIG. 4 shows bag management system 30 with each of shelves 32, 34, 36and 38 rotated down and no supply bags 40 loaded. FIG. 5 shows bagmanagement system 30 with lower shelf 32 folded down and shelves 34, 36and 38 rotated upwardly and out of the way to provide access to bottomshelf 32. In an embodiment, the shelves are configured in a cascading ortelescoping manner such that third shelf 36 can fold or rotate intoupper shelf 38, second shelf 34 can fold or rotate into third shelf 36and lower shelf 32 can fold or rotate into second shelf 34. The hingesof the shelves can have releasably interlocking apparatuses (e.g.,mating tabs and detents) that hold the shelves releasably in place whenfolded or rotated upwardly. Alternatively or additionally, the shelvescan releasably lock one to another, e.g., third shelf 36 locking toupper shelf 38, second shelf 34 locking to third shelf 36, and so on.For example, interlocking tabs and detents 42 and 44, respectively, areprovided at the sides or gussets of the shelves so that the lockingmechanisms 42 and 44 do not interfere with the bags 40 when loaded.

FIG. 6 shows bag management system 30 with lower shelf 32 folded down, afirst supply bag 40a loaded onto lower shelf 32, and shelves 34, 36 and38 hinged upwardly and out of the way. FIG. 7 shows bag managementsystem 30 with lower shelf 32 and second shelf 34 folded down, firstsupply bag 40 a loaded onto lower shelf 32, a second supply bag 40 bloaded onto second shelf 34, and shelves 36 and 38 hinged upwardly andout of the way.

FIG. 8 shows bag management system 30 with lower shelf 32, second shelf34 and third shelf 36 folded down, first supply bag 40 a loaded ontolower shelf 32, second supply bag 40 b loaded onto second shelf 34, athird supply bag 40 c loaded onto third shelf 36, and shelve 38 hingedupwardly and out of the way. FIG. 9 shows bag management system 30 withlower shelf 32, second shelf 34, third shelf 36 and top shelf 38 allfolded down, first supply bag 40 a loaded onto lower shelf 32, secondsupply bag 40 b loaded onto second shelf 34, third supply bag 40 cloaded onto third shelf 36, and fourth supply bag 40 d loaded onto topshelf 38.

Each tray in the bag management system 30 folds up providing easy accessto the shelf below. When used with cart 12 above, system 30 minimizesthe height to which patients have to lift the solution bags. The shelfholds solution bags 40 elevationally above a heater, which can belocated at the bottom of instrument 12 for example, and orients the bagso that the bag outlet port resides below the rest of the bag. Theconfiguration causes dialysis fluid to flow from the bags until empty,leaving any air trapped in the empty bags. This shelf configuration, bagplacement and orientation can enhance the volumetric pumping speed andaccuracy of the fluid delivery pumps when fluid is pumped directly fromthe supply bags, e.g., through an inline heater, and into the patientsince air does not flow downhill, e.g., from a bag 40 into a pumpingchamber of cassette 28.

One or more or all of shelves 32 to 38 can employ a sensor operable witha sensing system stored in memory. The sensor and associated systemperform multiple functions. One function is to determine if a dualchamber or multiple chamber bag has been opened to allow two or moreconcentrates to mix to form a dialysis fluid that can be pumped to thepatient. Sensing a properly opened bag can be a prerequisite for thepumps and/or valves or occludes to operate. The sensors can also detectwhich shelves 32 to 38 have bags and which do not and thus whetherenough fluid has or can be connected. One suitable sensor and associatedsystem is found in copending patent application Ser. No. 11/773,501,filed Jul. 5, 2007, entitled, “Apparatus and Method For Verifying A SealBetween Multiple Chambers”, assigned for the eventual assignee of thepresent disclosure, the entire contents of which are hereby incorporatedby reference and relied upon. An alternative inductive sensing apparatusand method is discussed below beginning at FIG. 35.

Disposable Set

Referring now to FIGS. 10 and 11, an embodiment of a disposable set 50for system 10 is illustrated. FIG. 10 illustrates that disposable set 50includes disposable cassette 28 and supply bags 40 as discussed above.Bags 40 in an embodiment each include a solution line or pigtail 46 a to46 d (referred to herein collectively as pigtails 46 or generally,individually as pigtail 46), which connect to a first set 48 a of supplylines. Solution lines or pigtails 46 in one embodiment terminate infemale connectors 56 protected by tip protector 66 a. Connectors 56 inone embodiment are female connectors protected by a pierceable cover.Disposable set 50 can include a second set of supply lines 48 b for ahigh-volume therapy as discussed below. First and second supply linesets each include multiple lines ending in a connector 58 protected by atip protector 66 b. Connectors 58 can be male spike connectors thatspike through the protective covers of female connectors 56 of bag lines46.

Disposable set 50 also includes a patient line 52 and drain line 54.Patient line 52 can be a dual lumen line in which one line terminates ina pierceably sealed female connector 56 protected by a tip protector 66a and the other line terminates in a spike connector 58 protected by atip protector 66 b (see FIGS. 15A to 15D). Drain line terminates in oneembodiment with a spike receptacle less a septum, so that a supply bagcannot be connected to the drain line.

Pigtails 46 in one embodiment terminate in female connectors 56protected by tip protector 66 a. Connectors 56/tip protectors 66 a areheld together in a single organizer in one embodiment. Patient line 52can be a single lumen patient line (batch dialysis) or a dual lumenpatient line (for batch or continuous dialysis) as desired. The firstset of supply lines 48 a, patient line 52 and drain line 54 are eachconnected to cassette 28.

FIG. 10 further illustrates one embodiment for a high volume disposableset (e.g., eight bags), which is provided by teeing a second set ofsupply lines 48 b off of the first set of supply lines 48 a (connectedto cassette 28) and providing an organizer for holding four spikeconnectors 58 on the end of each supply line 48 a or 48 b. The spikesand organizers can be integrated into a single molded spike bundle thatcontains the spikes and features for gripping and holding the bundleduring set up and operation. Each spike connector 58 of each supply linecan connect fluidly and sealingly with a female connector 56 at the endof each supply bag pigtail 46. As mentioned, each spike connector 58 isprotected by its own tip protector 66 b. Line clamps 62 are provided onthe first set of supply lines 48 a. The clamps can be used to occludethe first set of supply lines 48 a before an auto-connection mechanism(discussed below) disconnects connectors 58 of the first set of supplylines 48 a from connectors 56 at the end of pigtails 46. Theauto-connection mechanism can then connect the second set of supplylines 48 b to a second set of supply bags 40 (not illustrated).

FIG. 11 illustrates a second embodiment for producing a high-volumedisposable set 50. Here the first set of supply tubes 48 a is convertedto a high volume set via four-to-one manifold 60. Four-to-one manifold60 in one embodiment has at one end the same organizer holding fourlines 48 c terminating in spike connectors 58/tip protectors 66 b asthat described above for the supply lines 48 a and 48 b. Manifold 60 cantherefore itself be connected to up to four supply bags 40. A connector56/tip protector 66 a of a single input line 64 from four-to-onemanifold 60 is then inserted into the auto-connection mechanism (shownbelow) in lieu of the connector 56/tip protector 66 a at the end ofpigtail 46 of a single supply bag 40. An auto-identification systemshown below automatically tracks the number of bags connected to eachfour-to-one manifold 60 and the volume of the solution that has beenconnected. Disposable set 50 using manifold 60 can operate with up tosixteen, e.g., six liter, bags of solution.

Auto-Connection

Referring now to FIG. 12, instrument 20 in an embodiment includes pinchclamps or pinch valves 68 a to 68 d (referred to collectively herein asvalves 68 or generally, individually as valve 68), one valve 68 for eachpigtail 46 a to 46 d of supply bags 40 a to 40 d, respectively (ormanifold line 64 of four-to-one manifold 60). Clamps 68 a to 68 d arepositioned to hold and occlude pigtails 46 a to 46 d, respectively, when(i) connectors 56 at the end of the pigtails 46 are attached to astationary connector holder 70 and (ii) the tip protectors 66 aprotecting each connector 56 are attached initially to a tip protectorremoval carriage 72 of the auto-connection mechanism. Tip protectorremoval carriage 72 is also configured to remove spike connector 58 tipprotectors 66 b as shown below. Pinch clamps or valves 68 are opened,e.g., sequentially, to allow fluid to be withdrawn sequentially fromsupply bags 40. Clamps 68 in an embodiment are closed automatically ifthere is a need to reload cassette 28 after supply bags 40 have beenconnected. Stationary holder 70 holds supply bag pigtail connectors 56stationary during the auto-connection process.

FIG. 12 also illustrates a moveable connection carriage 74, which holdsthe organized spike connectors 58/tip protectors 66 b at the end ofsupply lines 48 a connected to cassette 28. The individual holders ofstationary holder 70 and moveable carriages 72 and 74 are aligned in theZ-direction as shown by the coordinate system in FIG. 12.

Moveable carriage 72 moves in the +X and −X directions to remove tipprotectors 66 a from connectors 56 and tip protectors 66 b from spikeconnectors 58. Moveable carriage 72 also moves in the +Y and −Ydirections to pull the removed tip protectors 66 a and 66 b out of theway for line connection and possibly to reload the tip protectors.Moveable carriage 72 in an embodiment uses to an XY gantry system, whichincludes a pair of lead screws each driven by a motor, such as a steppermotor. For example, moveable carriage 72 can be threaded and receive aball screw supported on two ends by bearings and driven by a steppermotor to move carriage 72 back and forth in a precise manner in the +Xand −X directions. That X-direction assembly can in turn be threaded,e.g., at a bearing support, and receive a ball screw supported on twoends by bearings and driven by a stepper motor to move the X-directionassembly (including carriage 72) back and forth in a precise manner inthe +Y and −Y directions.

Moveable carriage 74 moves in the +X and −X directions to push spikeconnectors 58 of cassette supply lines 48 a into sealed communicationwith pierceably sealed female connectors 56 of bag pigtails 46. Here,moveable carriage 74 can be threaded and receive a ball screw supportedon two ends by bearings and driven by a stepper motor to move carriage74 back and forth in a precise manner in the +X and −X directions.

System 10 is computer controlled and can for example include masterprocessing and memory operating with delegate controllers includingdelegate processing and memory. Master processor and memory can alsooperate with a safety controller having safety processing and memory. Inone embodiment, master processing and memory operates with a delegatemotion controller having processing and memory (e.g., programmable orvia an application specific integrated circuit (“ASIC”)), which outputsto the stepper motors and receives inputs, e.g., positional inputs fromposition sensors.

Referring now to FIGS. 13A to 13J, an auto-connection sequence for thesealed mating of connectors 56 of pigtails 46 of supply bags 40 to thespike connectors 58 of the supply lines of set 48 a (alternativelysupply line set 48 b and 48 c as discussed above) of cassette 28 isillustrated. In FIG. 13A, an organizer holding four spike connectors58/tip protectors 66 b of cassette supply line set 48 a connected tocassette 28 are loaded into the group holder of moveable carriage 74.Alternately, an integrated four-spike bundle with connectors 58/tipprotectors 66 b is loaded into the group holder of moveable carriage 74.In this step, cassette 28 is also loaded into instrument 20 (see FIGS. 2and 3).

In FIG. 13B, connectors 56/tip protectors 66 a located at the end offour supply bag pigtails 46 are loaded into individual holders ofstationary holder 70 and moveable carriage 72. In particular, connectors56 are loaded into individual holders of stationary holder 70 and tipprotectors 66 a are loaded moveable carriage 72. Thus in FIG. 13B, tipprotectors 66 a and 66 b are set to be removed automatically fromconnectors 56.

After spike connectors 58/tip protectors 66 b and connectors 56/tipprotectors 66 a have been loaded into the auto-connection mechanism, acover or door is closed (not illustrated), isolating holder 70,carriages 72 and 74, spike connectors 58/tip protectors 66 b and femaleconnectors 56/tip protectors 66 a from the environment. System 10 theninjects filtered high-efficiency-particulate-air (“HEPA”) orultra-low-penetration-air (“ULPA”) into the sealed compartment to reducethe bioburden in the region prior to tip protector removal fromconnectors 56 and 58. Pneumatic control of HEPA or ULPA air can belocated on the motion controller mentioned above or on a separatepneumatic controller operating with the master controller.

The imaging system determines which supply bags have been loaded(quantity, size, solution type, expiration date, lot code, etc.) andalerts the user if a problem arises with any of the above identifiers.For example, the solution volume may be insufficient to perform theselected therapy. Alternatively, a connector may be distorted or damagedso that it will not connect properly.

In FIG. 13C, moveable carriage 72 moves in the −X direction (accordingto coordinate system of FIG. 12) to remove pre-loaded tip protectors 66a from supply bag connectors 56.

In FIG. 13D, moveable carriage 72 moves further in the −X direction(according to coordinate system of FIG. 12) to lock tip protectors 66 bto protecting spike connectors 58.

In FIG. 13E, moveable carriage 72 moves in the +X direction (accordingto coordinate system of FIG. 12) to remove tip protectors 66 b fromspike connectors 58.

In FIG. 13F, moveable carriage 72 moves in the +Y direction (accordingto coordinate system of FIG. 12) to move out of the way of supply bagconnectors 56 and spike connectors 58.

In FIG. 13G, moveable carriage 74 moves in the +X direction (accordingto coordinate system of FIG. 12) towards stationary holder 70 to pushspike connectors 58 into pierceably sealed supply bag connectors 56 andto make sealed supply bag 40 to cassette 28 connections. After theconnections of spike connectors 58 to supply bag connectors 56 have beenmade, an imaging system described below verifies that the connectionshave been made properly and that no leaks are present.

FIG. 13H(a) shows one removal embodiment in which a connected supply ofset lines 48 a and solution lines or pigtails 46 and associated emptysupply bags 40 and cassette 28 are removed from carriage 74 and holder70, respectively, together. In FIG. 13I, moveable carriage 72 is thenmoved in the −Y direction (FIG. 12) to allow the consumed tip protectors66 a and 66 b to be retrieved.

FIG. 13H(b) shows another removal embodiment in which moveable carriage74 moves in the −X direction to pull connectors 56 and 58 apart, afterwhich moveable carriage 72 moves in the −Y direction (according tocoordinate system of FIG. 12) and then back and forth in the + and −Xdirections to reattach tip protectors 66 a and 66 b to connectors 56 and58, respectively, allowing supply lines of set 48 a, pigtails 46 andassociated supply bags 40 and cassette 28 to be removed from carriages72 and 74 and holder 70, respectively. This latter removal method ispreferable if it is common that the supply bags will not be completelyempty when the bags have to be removed.

Auto-Identification

FIG. 14 illustrates one embodiment for an auto-identification system.The system includes a color-capture device (“CCD”) camera 80, which usesa charge-coupled device image sensor and an integrated circuitcontaining an array of linked, or coupled, light-sensitive capacitors.Other cameras that create a three-dimensional image of a connection areashown in FIG. 14 may be used alternatively. The auto-identificationsystem uses the image from camera 80 to determine characteristics ofsolution bags 40 and to verify that the correct, undamaged connectors 56and 58 are loaded into the mechanism.

The auto-identification system accomplishes solution identification viaa character recognition routine (located for example on the motioncontroller or a separate video controller operable with the centralprocessing unit or master controller) that “reads” the codes printed onthe pigtail connectors 56 connected to supply bags 40. The “codes”provide (i) solution type, e.g., glucose or bicarbonate concentrate orpremixed dialysate, (ii) bag volume, e.g., six liters, and (iii) numberof bags per connector 56, e.g., single bag or multiple bags viafour-to-one manifold 60. The image of each connector 56 is comparedagainst stored images of the range of acceptable geometries forconnector 56. A deformed connector, or a connector that has been loadedincorrectly, or that does not match therapy prescription will falloutside of a range of acceptable geometries and cause system 10 tosignal an alarm and cause other appropriate action, e.g., closing clamps68 or not allowing them to be opened until the alarm is cleared. Theimaging system also verifies that the “connected” joints fall within anacceptable range of geometries for a good joint connection. If a jointleaks and droplets form, the imaging system sees the droplets and causesan alarm.

Priming

In an embodiment, a dual lumen patient line 52 (FIG. 10) is used. Onelumen is connected to a patient-drain port through a pumping chamber ofdisposable cassette 28. The other lumen is connected to a patient-fillport through a different pumping chamber of the disposable cassette 28.During priming of the patient line, the two lumens of the patient lineare connected together. Cycler 20 causes one of the diaphragm pumps ofcassette 28 to pump or push fresh fluid out the patient-fill port on thedisposable cassette 28, down one lumen of patient line 52, until itreaches the end of the patient line. The fresh fluid is then pumped backup the other lumen of patient line 52, into cassette 28 through thepatient-drain port and into another diaphragm pump of cassette 28, whichremoves air that the fluid pushes through the patient line 52. Whenfluid fills the second pump chamber, the patient line is fully primed.

Patient Connection/Disconnection

Primed dual lumen patient line (with fill lumen 52 a and drain lumen 52b connected) and transfer set 82 (with fill line 84 and drain line 86connected) are loaded into a patient line an auto-connection device 90illustrated in FIGS. 15A to 15E. Device 90 can be separate from orintegrated into instrument 20. Instrument 20 or cart 12 in an embodimentprovides an area and apparatus for storing device 90. Device 90 can bepowered or configured for manual or manual/automatic operation. Device90 includes a stationary portion 92 and a portion 94 rotatable andtranslatable with respect to stationary portion 92.

As seen in FIG. 15E, device 90 includes a cover 91 and base 93 whichmate (e.g., hingedly or separately) to enclose connectors 56 (withpierceable membrane ) and 58 (spike) of lumens 52 a and 52 b and lines84 and 86 when loaded into portions 94 and 96. Cover 91 and base 93 canbe plastic or metal as desired. FIG. 15E also illustrates that device 90includes one or more motor 95 having an output shaft 97 connectedoperably to portion 94 to rotate and/or translate portion 94 relative toportion 92. For example, output shaft 97 of motor 95 can drive a ballscrew that in turn is connected threadingly to portion 94, which enablesmotor 95 to translate portion. In the illustrated embodiment, outputshaft 97 of motor 95 is coupled to portion 94 in a manner such thatmotor 95 can rotate portion 94. A lever 99 is connected to thesubassembly of motor 95 and moveable portion 94, such that the patientor caregiver can translate portion 94 back and forth with respect tostationary portion 92 via lever 99. Device 90 is alternatively fullyautomatic (e.g., AC or battery powered) or fully manual.

Device 90 also includes an apparatus for maintaining an asepticenvironment when lumens 52 a and 52 b and lines 84 and 86 are pulledapart. For example, device 90 can employ an ultraviolet (“UV”) light orradiator described in U.S. Pat. Nos. 4,412,834 and 4,503,333, owned bythe eventual assignee of the present application, the entire contents ofwhich are incorporated herein by reference. Device 90 can also introduceHEPA or ULPA filtered air into the volume around the connector prior toconnection.

Referring additionally to FIGS. 15A to 15D, once the dual lumen patientline 52 and transfer set 82 are loaded into device 90, the patient lineshown here as having fill lumen 52 a (terminating in a female connector56 as described above) and drain lumen 52 b (terminating in a spikeconnector 58 as described above) are split apart and connected to thepatient's transfer set 82. Transfer set 82 includes a fill line 84(terminating in a spike connector 58) and a drain line 86 (terminatingin a female connector 56).

In FIG. 15A, fill lumen 52 a is connected via the prime sequence todrain lumen 52 b. Fill line 84 and drain line 86 or transfer set 82 arealso connected. Mated connectors 56 and 58 of each pair are loaded intodevice 90, such that return lumen 52 b and fill line 84 (both havingspike connectors 58) are loaded into stationary portion 92 of device 90and fill lumen 52 a and drain line 86 (both having female connectors 56)are loaded into rotatable portion 94 of device 90. In one embodimentportions 92 and 94 are structured such that portion 92 can only acceptspike connectors 58 and portion 94 can only accept female connectors 56.Cover of device 90 is closed and the aseptic apparatus is initiated orenergized.

In FIG. 15B, portion 94 via, e.g., electrically actuated stepper motor95 coupled to a ball screw (not illustrated), or solenoid (notillustrated), pulls lumens 52 a and 52 b and lines 84 and 86 apart,respectively. Portion 90 includes a carriage holding connectors 56 oflumen 52 a and line 86, which are pulled apart from spike connectors 58.Translatable portion 94 and motor can be housed completely within device90 and sealed from the outside environment.

In the illustrated embodiment, the translator is operated manually vialever 99 that the patient grabs and translates to translate portion 94carrying connectors 56 of lumen 52 a and line 86 towards/away from spikeconnectors 58. In the illustrated embodiment, a thinner shaft of lever99 is sealed to device 90, such that the handle portion of lever 99remains outside device 90 and is configured for the patient to grasp andmove comfortably. The shaft of lever 99 is connected to motor 95, whichin turn is coupled to portion 94 holding connectors 56 of lumen 52 a andline 86.

In FIG. 15B, the aseptic apparatus of device 90 continues to beenergized to prevent the tips of connectors 56 and 58 from becomingcontaminated.

In FIG. 15C, motor 95 rotates rotatable portion 94 holding femaleconnectors 56 one-hundred-eighty degrees relative to stationary spikeportion 92, such that now return lumen 52 b of dual lumen patient line52 is aligned with drain line 86 of transfer set 82. Also now, filllumen 52 a of dual lumen patient line 52 is aligned with fill line 84 oftransfer set 82. The aseptic apparatus of device 90 continues to beenergized to prevent the tips of connectors 56 and 58 from becomingcontaminated.

In FIG. 15D, translatable portion 94 (electric or manual) pushes filllumen 52 a of dual lumen patient line 52 towards fill line 84 oftransfer set 82, connecting spike connector 58 to female connector 56.Simultaneously, return lumen 52 b of dual lumen patient line 52 isconnected sealingly and operably with drain line 86 of transfer set 82.System 10 can now perform an initial patient drain to remove the priorprocedure's spent last-bag fill and ready the patient for a first fillof the present therapy.

It should be appreciated that the sequence of FIGS. 15A to 15D works nomatter which side 96 or 98 of device 90 that connected lumens 52 a and52 b and connected lines 84 and 86 are loaded in FIG. 15A.

In a patient disconnection sequence, connected inflow lines 52 a and 84are loaded into one side 96 or 98 of device 90. Connected outflow lines52 b and 86 are loaded into the other side of device 90. In a next step,device 90 (manually or automatically) disconnects cassette inflow line52 a from transfer set inflow line 84 and cassette outflow line 52 bfrom transfer set outflow line 86.

Next, rotatable portion 94 holding female connectors 56 is rotatedone-hundred-eighty degrees relative to stationary spike portion 92, suchthat now return lumen 52 b of dual lumen patient line 52 is aligned withfill lumen 52 a of dual lumen patient line 52, and drain line 86 oftransfer set 82 is now aligned with fill line 84 of transfer set 82.

In a next step, device 90 (manually or automatically) connects cassetteinflow line 52 a to cassette outflow line 52 b and transfer set inflowline 84 to transfer set outflow line 86. Device 90 provides an asepticenvironment for the above four steps. The patient can then remove theconnected dual lumen line 52 and transfer set 82 from device 90 and isfree from the dialysis instrument.

It should be appreciated that device 90 is not limited to the dual lumenpatient line 52/transfer set 82 connection/disconnection applicationjust described or even to APD. For example, a single patient line 84having a spike connector 58 protected by a female cap 56 could be loadedinstead into side 98 of device 90, while a supply bag pigtail 46 havinga female pierceable connector 56 and a cap is loaded into side 96 ofdevice 90. The female cap 56 is next removed from male-ended patientline 84, while a cap is removed from female-ended supply pigtail 46simultaneously from its cap (by pulling rotatable portion 94 away fromspike portion 92). Next, rotatable portion 94 is rotated with respect tospike portion 92. Afterwards, female portion 94 is slid towards spikeportion 92, mating spike connector 58 of patient line 84 with femaleconnector 56 of supply bag pigtail 46, thus connecting a supply bag 40to the patient, for example for CAPD. A similar connection could be madeconnecting the patient to pumping cassette 28.

Patient Drain and Fill

During patient drain, system 10 removes effluent from the patientthrough return lumen 52 b of dual lumen patient line 52. When drain iscompleted and system 10 advances to a fill cycle, system 10 deliversfresh fluid to the patient through fill lumen 52 a of dual lumen patientline 52. Here, the only effluent that is “recirculated” back to thepatient is the small volume of effluent in fill line 84 of transfer set82 and the patient's catheter. Even this volume need not be recirculatedto the patient if a dual lumen catheter and transfer set is used.Further, if a dual lumen catheter and dual lumen transfer set is usedwith system 10, system 10 can perform a multiple pass continuous flowperitoneal dialysis (“CFPD”) therapy. The multiple pass CFPD therapy canemploy a single fill, with a long recirculating flow dwell, or the CFPDtherapy can be tidal in nature and recirculate flow during at least oneof the dwell periods.

Cassette Improvements

Referring now to FIG. 16, cassette 100 illustrates one embodiment of acassette and method of making same, in which a rigid plastic portion 110of the cassette is encapsulated within cassette sheeting 102. However,sheeting 102 is not welded to the sides of the rigid portion 110,sheeting 102 is instead welded to itself. Plastic portion 110 in oneembodiment is rigid and made of acrylonitrile butadiene styrene (“ABS”),acrylic, polyolefin, polycarbonate, polyethylene or polypropylene.Sheeting 102 in one embodiment is flexible, e.g., for flexing to pumpliquid, and opening and closing valve chambers. Sheeting 102 can be madeof polyvinyl chloride (“PVC”), polyethylene, kraton or polyolefin. Also,two or more plies of the different or same materials can be used,wherein the grains of the plies can flow perpendicular to each other toincrease strength and minimize the potential for slits, holes and tears.For example, the outside layer opposite the cassette can have goodabrasion, puncture and tear resistant properties and a middle layerhaving good strength properties.

Sheeting 102 is folded to produce a first side 104 a, a second side 104b, a folded top 106 and edges 108 a to 108 c as illustrated. Foldedsheet 102 is slid over rigid portion 110 as shown in FIG. 16. Next, sideedges 108 a of sides 104 a and 104 b are welded together and aroundsupply lines 48, patient lines 52 or drain line 54. Alternatively, edges108 a of sides 104 a and 104 b are welded together and around portsextending from rigid portion 110 (not seen in FIG. 16), to which supplylines 48, patient lines 52 or drain line 54 are fitted sealingly. Bottomedges 108 b of sides 104 a and 104 b are welded together. Side edges 108c of sides 104 a and 104 b are welded together. Flexible sheeting 102 inthis manner forms a sealed pouch around rigid portion 110. Sides 104 aand 104 b are alternatively separate sheets welded together along foursides.

Rigid portion 110 includes or forms pump chambers 112. As shown below,an alternative cassette includes three pump chambers. Rigid portion 110in the illustrated embodiment also includes a plurality of valvechambers 114. Pump chambers 112 and valve chambers 114 each includeridges 116 defining the respective pump or valve chamber, which extendoutwardly from a base wall 118 of rigid portion 110. The opposite sideof rigid portion includes ridges 116 extending in the other directionfrom base wall 118 and defining flow paths (not seen) that communicatewith the pump chambers 112 and valve cambers 114.

In operation, side 104 a of sheeting 102 needs to be sealed to ridges116 of the pump and valve chambers for the pneumatic movement andcontrol of fluid. A dialysis instrument operating with pouch cassette100, which has sheeting 102 sealed to itself around rigid portion 110(and to the tubes as discussed above) but not directly to raised ridges116, applies a positive pressure across the surface 104 a relative torigid portion 110. The positive pressure seals surface 104 a to theraised ridges 116 temporarily during operation so that pumps 112 andvalves 114 can function properly. Positive pressure is also provided onreverse surface 104 b of sheeting 102 to compress surface 104 b toraised ridges 116 of the flow paths (not seen). The positive pressurecan be provided pneumatically, e.g., via an inflatable bladder, and/ormechanically, e.g., via spring biasing, solenoid actuation and/or theclosing of a door behind which cassette 100 is loaded.

FIG. 16 also shows that base wall 118 can include instrument loading andlocating holes 120, which enable a locating guide 122 to be snapped inplace after sheeting 102 has been welded to itself and to tubing 48, 52and 54. In an embodiment, sheeting 102 is welded via a heat sealprocess, which uses a die. That same die can also punch aligning holes124 through sheeting 102 to facilitate the installation of theloading/locating guide 122.

Cassette 100 includes integrated valve ports 114. System 10 of FIGS. 1to 3 and instrument 20 of FIG. 12 show line clamps 68 external to thecassette, which occlude associated tubing. Pinch valves 68 allow system10 to access each of the supply lines independently but also toeliminate the need for the manual clamps that are typically present oncassette supply lines 48. Machine 20, not the user, occludes supplylines 48 when it is necessary to do so, for example when bag connectionsare made, and opened to perform the therapy. Supply lines 48 also needto be occluded after many alarm/failure conditions or if the powerfails.

The pinch valves 68 also aid in the drawing of fluid from the solutionlines 46. For example, the pinch valve 68 to only the top shelf 38 canbe opened, allowing bag 40 d to drain partially, e.g., more than 50%,before opening valve 68 to supply bag 40 c on the second-to-top shelf 36allowing bag 40 c to drain partially, e.g., more than 50%, beforeopening valve 68 to supply bag 40 b on the third-to-top shelf 34,allowing bag 40 b to drain partially, e.g., more than 50%, beforeopening valve 68 to supply bag 40 a on bottom shelf 32. Fluid will flowvia gravity into the pumps and air will tend to float to the back ofeach bag 40. Using this sequence, all of supply bags 40 can be emptiedwithout sucking any air into the solution lines 46. If all supply lines48 are opened at once, lower bags 40 a and 40 b will become bloated dueto the weight of fluid from the upper supply bags 40 c and 40 d.

It should be appreciated that flexible pouch cassette 100 can includevalve chambers 114 or not include valve chambers 114 if the abovedescribed pinch clamps 68 are used instead. Further, it should beappreciated that the apparatuses and methods disclosed in connectionwith system 10 and instrument 20 are not limited to use with pinchclamps 68 and instead can be used with valve chambers 114 discussedabove. Further alternatively, system 10 can operate with a combinationof valve chambers 114 and pinch clamps 68, e.g., using cassette-basedvalve chambers 114 during treatment and pinch clamps 68 during setup andalarm conditions.

Referring now to FIGS. 17A, 17B, cassette 130 illustrates one embodimentof a three pump chamber disposable pumping and valving cassette. FIGS.18A to 18C illustrate three methods for operating the three pumpchambers to achieve desired outputs.

Cassette 130 in the illustrated embodiment includes many of the samestructures or types of structures as cassette 100, such as rigid portion110 having a base wall 118 with ridges 116 extending from the base wall118 to form pump chambers 112 a to 112 c (referred to hereincollectively as chambers 112 or generally, individually as chamber 112).Ridges 116 also define valve chambers 114 as described above.Alternatively, cassette 130 with three valve chambers 112 operates withpinch clamps 68 and does not use or provide valve chambers 114.

FIG. 17B illustrates the back side of cassette 130. Here, ridges 116extending from base wall 118 define a flow path 132. Flow path 132includes manifold sections 134 a and 134 b and baffled sections 136 a to136 f extending between manifold sections 134 a and 134 b. Manifoldsections 134 a and 134 b and baffled sections 136 a to 136 f of flowpath 132 enable cross-talk between pump chambers 112, so that the flowpatterns discussed below in connection with FIGS. 18A to 18C can beachieved as shown in more detail below in connection with FIG. 17C.

Cassette 130 includes flexible sheeting 104 a and 104 b as discussedabove. Sheeting 104 a and 104 b can be separate sheets welded or bondedto the sides of rigid portion 110 and ridges 116 of pump chambers 112and valve chambers 114. Alternatively, sheeting 104 a and 104 b isprovided via a single sheet 102 shown above, which includes a foldededge 106 and welded or bonded edges 108 a to 108 c as shown anddescribed in connection with FIG. 16.

FIG. 17C illustrates one possible valve arrangement for the three pumpcassette 130 of FIGS. 17A and 17B. FIG. 17C illustrates the portsextending out the bottom of cassette 130, which is one preferablearrangement for air handling because any air in cassette will tend torise to the top of the cassette, leaving only fluid to exit the cassettefrom the bottom. Boxes marked “A” are areas of cassette 130 thatinteract with air sensors located within instrument 20. Boxes marked “T”are areas of cassette 130 that interact with temperature sensors locatedwithin instrument 20. The Box marked “C” is an area of cassette 130 thatinteracts with a conductivity sensor located within instrument 20.

As illustrated, cassette 130 includes six supply ports, a dedicatedto-patient port, a to/from-patient port, a drain port, and an additionalport for mixing, further supply or sending or receiving fluid from abatch heater. Cassette 130 includes three pump chambers 112 a to 112 cdescribed above. Valves 114 in FIGS. 17A and 17B are differentiated viavalves V1 to V28. The following valve states are merely examples showingdifferent flow regimes achievable via cassette 130.

Filling the patient with a premixed solution can for example occur byallowing fresh mixed solution into cassette 130 via valve V16, flowingthrough the heater via valve V1 into pump chamber 112 c. At the sametime, pump chamber 112 b pushes the same fluid to patient via openvalves V10, V15, V27 and the to/from patient port valve. In this regime,to-patient port and valve are not needed. At the same time, pump chamber112 c can be performing a volume measuring determination as discussedbelow. In an alternative embodiment, dedicated to-patient port and valveare used as a second outlet to the patient.

Draining effluent from the patient can for example occur by allowingeffluent into cassette 130 via to/from patient valve and port, flowingthrough valves V26 and V12 into pump chamber 112 a. At the same time,pump chamber 112 b pushes the effluent to drain via open valves V4 andthe drain valve. In this regime, dedicated to-patient port and valve arenot needed. At the same time, pump chamber 112 a can be performing avolume measuring determination as discussed below. In an alternativeembodiment, temperature sensor access valve V15 can be openedsimultaneously to allow temperature of the effluent entering chamber 112a to be sensed.

In a concentrate mixing regime, chamber 112 c can be filling fromconcentrate supply 1 through valves V17 and V7. Chamber 112 b can befilling from concentrate supply 2 through valves V20 and V9. Chamber 112a, here acting as an accumulator as described below in FIG. 18C, outputsmixed concentrates via valves V5 and V16 to a mixer, for example. In analternative embodiment, a separate mixer is not used, the length of thepatient line is sufficient to mix the concentrates, and chamber 112 aoutputs alternatively through valves V5, V28, V27 and the to/frompatient valve collectively to the patient.

In a second stroke as described below in FIG. 18C, chambers 112 c and112 b empty half of their respective concentrates through valves V1 andV3, respectively and V5 collectively into chamber 112 a. At the sametime, chambers 112 c and 112 b the other half of their respectiveconcentrates through valves V1 and V3, respectively and valve V16collectively to a mixer. In an alternative embodiment, a separate mixeris not used, the length of the patient line is sufficient to mix theconcentrates, and chambers 112 c and 112 b the other half of theirrespective concentrates alternatively through valves V1 and V3,respectively and valves V28, V27 and the to/from patient valvecollectively to the patient.

In a multi-pass flow regime, chamber 112 c fills with fresh, e.g.,premixed, solution from supply 1 through valves V17 and V7. At the sametime, chamber 112 b empties fresh to the patient via valves V3, V28 andthe to-patient valve to the patient. At the same time, chamber 112 afills with effluent from the patient via the to/from patient valve, andvalves V26 and V12. Here, the fluid can be recirculating because thereis no net fluid loss or ultrafiltration (“UF”) taking place.

In a UF to drain mode multi-pass flow example, chamber 112 c emptiesfresh to the patient via valves V1, V28 and the to-patient valve to thepatient. At the same time chamber 112 b fills with effluent from thepatient through the to/from patient valve, and valves V26 and V10. Atthe same time, chamber 112 a empties effluent to drain via valve V6 andthe drain valve. In an alternative UF to bag to bag multi-pass mode,chamber 112 a alternatively empties effluent to an empty supply bag,e.g., supply 3 via valves V11, V24 and V25.

In a second state of the UF bag to bag multi-pass mode, chamber 112 cfills with fresh, e.g., premixed, solution from supply 1 through valvesV17 and V7. At the same time, chamber 112 b empties fresh to the patientvia valves V3, V28 and the to-patient valve to the patient. At the sametime, chamber 112 a fills with effluent from the patient via the to/frompatient valve, and valves V26 and V12.

A test can be run to see if a dual or multi-chamber bag has been openedproperly. Here one of pump chambers empties fluid to drain, flowing thefluid past conductivity sensor (“C”), which checks to see if theconductivity measured is indicative of a properly mixed solution, inwhich case therapy can proceed, and an improperly mixed case in which analarm is generated.

FIG. 18A illustrates one pumping sequence for pump chambers 112 in whicha chamber fill stroke (black segments) is slightly shorter in durationthan a chamber empty stroke (diagonal segments), which are separated byrelatively short fluid measurement periods (dotted segments). A fluidmeasurement (amount of fluid pumped) method is discussed in detailbelow. Also discussed below is a way to eliminate the fluid measurementperiods (dotted segments) occurring after the chamber empty strokes(diagonal segments).

In one embodiment, a pneumatic actuator applies negative and positivepressure to sheet 104 a to pump fluid into or out of one of pumpchambers 112. A pump controller, e.g., microprocessor and computerprogram memory, controls pneumatic actuators to apply positive, negativeor no pressure to the appropriate chamber 112 at the appropriate time.The processor cycles through a program which at any given time tells theprocessor which state each pump actuator should be in. The processorcontrols each actuator based upon that cycle.

Three pump cassette 130 provides continuous flow to the patient duringfill, while also drawing fluid continuously from the supply bag throughan inline heater for example. As seen in FIG. 18A, at any given time atleast one pump chamber 112 a to 112 c is delivering fluid to the patientor to an accumulator (one purpose for an accumulator is described belowin connection with FIG. 18C). At any given time at least one pumpchamber 112 a to 112 c is filling the patient with heated dialysate.

As seen in FIG. 18A, at time T1, pump chamber 112 a is at rest for ameasurement calculation from a previous emptying stroke, pump chamber112 b is emptying fluid to the patient, pump chamber 112 c is fillingwith fluid. At time T2, pump chamber 112 a is filling with fluid, pumpchamber 112 b is still emptying fluid to the patient, pump chamber 112 cis at rest for a measurement calculation from a previous filling stroke.At time T3, pump chamber 112 a is still filling, pump chamber 112 b isstarting a fill stroke, pump chamber 112 c is emptying. At time T4, pumpchamber 112 a is emptying, pump chamber 112 b is filling, pump chamber112 c is starting a rest period for measurement calculation. At time T5,pump chamber 112 a is still emptying, pump chamber 112 b is beginning toempty, pump chamber 112 c is filling. At time T6, pump chamber 112 a isfilling, pump chamber 112 b is emptying, pump chamber 112 c is filling.At time T7, pump chamber 112 a is still filling, pump chamber 112 b isstarting a rest period for measurement calculation, pump chamber 112 cis emptying. At time T8, pump chamber 112 a is starting an emptyingstroke, pump chamber 112 b is filling, pump chamber 112 c is emptying.At time T9, pump chamber 112 a is emptying, pump chamber 112 b isfilling, pump chamber 112 c is starting a fill stroke.

While the above sequence is described in connection with fresh fluideither filling the pump chambers 112 a to 112 c or emptying chambers 112to the patient, the same sequence can be employed in connection withspent fluid either filling the pump chambers 112 a to 112 c or emptyingchambers 112 to drain. In either case, filling and emptying pumpchambers 112 is continuous when the operation of the three chambers 112is superimposed.

FIG. 18B shows a similar sequence to that of FIG. 18A. Here, however,the overlap of the filling strokes and emptying strokes is the same.FIG. 18B illustrates that the relative durations of the filling andemptying strokes can be modified to suit a particular pump chamber andactuation configuration. FIGS. 18A and 18B also show that each time anemptying stroke is about to start, another emptying stroke already inprogress is going to stay in progress long enough such that the start ofthe empty stroke can be delayed for a short period of time, e.g., todischarge a small amount of air from the chamber about to start withoutdisrupting the continuity of the fluid emptying. For example, at time Tin FIG. 18B, pump chamber 112 a is supposed to start emptying eitherfresh fluid to the patient or spent fluid to drain. The start of thepump-out stroke could be delayed for a short period of time to dischargeair for example, without disrupting the continuous flow because pumpchamber 112 c still has some of its emptying stroke remaining.

FIG. 18C illustrates a sequence in which fluid is being mixed, e.g.,from two sources to make a stable dialysate for the patient. This can bedone for either PD or HD, either online or from bags or containers.Here, pump chambers 112 a and 112 b are synchronized. Pump chambers 112a and 112 b receive fresh fluid that has already been mixed in oneembodiment. Alternatively, pump chamber 112 a pumps one fluid, whilepump chamber 112 b pumps a second fluid, each to a same line in whichthe two fluids are mixed properly. Pump chamber 112 c is an accumulatorthat receives mixed fluid from pump chambers 112 a and 112 b. Pumpchamber 112 c outputs to the patient.

The system operating the sequence of FIG. 18C is valved or the flowpaths of the system are structured such that half of the mixed fluidleaving pump chambers 112 a and 112 b during the emptying stroke flowsto the patient, while the other half flows to fill pump chamber oraccumulator 112 c. When pump chambers 112 a and 112 b are filling,accumulator or pump chamber 112 c sends its mixed fluid volume to thepatient. Since all fluid flowing to and from accumulator 112 c has beenaccounted for in the measurement periods of pump chambers 112 a and 112b, separate measurement periods for pump accumulator 112 c are notneeded. Here, flow to the patient is continuous. Filling from theconcentrate sources is intermittent. A similar routine could be used toremove effluent from the patient. Accumulator 112 c is always attemptingto fill with effluent from the patient with this routine. When pumps 112a or 112 b fill, the pumps pull some fluid from accumulator 112 c aswell as from the patient. A routine such as one of FIG. 18A or FIG. 18Bcan also be used instead to pull effluent so that flow from the patientis continuous and smoother.

Cassette Interface Improvements

Referring now to FIGS. 19 to 22, pneumatic system 150 illustrates oneembodiment of a disposable cassette pumping interface of the presentdisclosure. System 150 includes a disposable cassette 140. Disposablecassette 140 is similar to cassettes 100 and 130 described above andincludes many of the same components, which are numbered the same.Cassette 140 includes a rigid housing or portion 110. Flexible sheets104 a and 104 b (not seen in FIG. 19) are welded or bonded to rigidportion 110. Alternatively, sheets 104 a and 104 b are formed from thesingle folded sheet 102 discussed above in connection with cassette 100.Cassette 140 is shown from the reverse side as that shown in FIG. 16 forcassette 100. Here, pump chambers 112 a and 112 b bulge outwardly,showing the reverse side of pump chambers 112 as shown in FIG. 16.Cassette 140 can alternatively include the third pump chamber 112 cdiscussed above in connection with cassette 130.

Cassette 140 includes a base wall 118 as described above. Ridges 116extend outwardly from base wall 118 to form a plurality of flow paths132. The valve chambers 114 and surfaces of pump chambers 112interacting with the cassette sheeting are provided on the opposite sideof cassette 140 than the side that is shown in FIG. 19. Cassette 140further includes a plurality of valve ports 126, which communicatefluidly with flow paths 132 and connect sealingly to tubes, such assupply tubes 48, patient line 52 and drain line 54 shown above forexample in connection with FIG. 16.

Pneumatic system 150 includes a membrane gasket 145, which is shown indetail in connection with FIGS. 20 and 22. Membrane gasket 145press-fits and seals in a plurality of places to a cassette manifold180, which is shown in detail in connection with FIGS. 20 and 21. Inparticular, cassette manifold 180 includes a interface plate 185, towhich membrane gasket 145 is attached and sealed.

Referring now to FIGS. 20 and 22, membrane gasket 145 is described indetail. Membrane gasket 145 is made of a suitable compressible andwatertight material, such as silicone rubber, ethylene propylene dienemonomer (“EPDM”) rubber, viton or other elastomers having a good fatiguelife. In one embodiment, membrane gasket 145 is made of compressionmolded silicone rubber. Membrane gasket 145 includes a side 146, whichinterfaces with, and indeed moves with, sheet 104 a of cassette 140.Membrane gasket 145 includes an opposite side 154, which interfaces withand seals in various places to interface plate 185.

Cassette side 146 of membrane gasket 145 includes raised pump ridges 148a and 148 b, which in an embodiment mate with and press seal againstraised ridges 116 shown for example in FIGS. 16 and 17A as forming theshape of pump chambers 112. A pneumatic bladder, e.g., contained in thedoor of instrument 20, can be inflated when the door is closed to pressa gasketed plate (not shown) against cassette 145 which, in turn,compresses sheeting 104 a of cassette 145 against raised ridges 148 aand 148 b, such that ridges 148 a and 148 b form an o-ring-like sealaround raised ridges 116 of pump chambers 112 of disposable cassette140. This seal is described in U.S. Patent Application No. 2004/019313A1, entitled, “Systems, Methods and Apparatus for Pumping Cassette BasedTherapies”, and U.S. Pat. No. 6,261,065, entitled, “Systems and Methodsfor Control of Pumps Employing Electrical Field Sensing”, both of whichare incorporated herein by reference and are assigned to the eventualassignee of the present disclosure.

Cassette facing surface 146 of membrane gasket 145 further includesraised ridges 152 forming an enclosed path which, in the same manner,seals around raised ridges 116 of valve chambers 114 of disposablecassette 140. FIG. 16 shows ten valve chambers 114, which are generallyaligned with and have the same shape as the ten enclosed ridges 152 ofcassette surface 146 of membrane gasket 145. Again, in an embodiment,enclosed ridges 152 mate with and press seal against ridges 116 of valvechambers 114 of the disposable cassette 140.

FIG. 22 illustrates the opposite surface 154 of membrane gasket 145,which faces and interacts with interface plate 185 of cassette manifold180. A raised rim 156 runs along the outside of surface 154, so that thegasket holds its shape. An inner plateau 158 also extends out fromsurface 154. The removal of material between plateau 158 and raised rim156 allows the two structures to move independently when the instrumentdoor is closed and cassette 140 is pressed between the instrument doorand membrane gasket 145, which is retained by interface plate 185.Raised rim 156 optionally seals about a raised edge 202 of interfaceplate 185, helping membrane gasket 145 to seal to the interface plateand prevent water or particle ingress.

Plateau 158 defines a pair of blind pump wells 160 a and 160 b. Blindpump wells do not extend all of the way through the thickness ofmembrane gasket 145. Instead, pump wells 160 a and 160 b each includesidewalls 162, which extend most of the way through the thickness ofmembrane gasket 145 but leave a thin wall 168. As described in detailbelow, thin walls 168 move with sheeting 104 of cassette 140 residingwithin pump chambers 112 a and 112 b of the cassette.

In a similar manner, plateau 158 defines a plurality of blind valvewells 164. Blind valve wells 164 likewise do not extend all of the waythrough plateau 158 of membrane gasket 145. Instead, blind valve wellsinclude sidewalls 166 that extend most of the way through plateau 158but terminate at blind wall 168. Blind wall 168 of blind valve wells 164in turn operate with sheeting cassette 104 a at valve chambers 114.

Membrane gasket 145 defines ports or apertures 170 that extend all ofthe way through plateau 158 of membrane gasket 145. Accordingly,apertures 170 are seen on both surfaces 154 of FIG. 22 and 146 of FIG.20. As further seen in FIG. 20, raised pump ridges 148 a and 148 b andraised valve ridges 152 on surface 146 of membrane gasket 145 enclose orencompass pneumatic ports 170. As discussed in detail below, pneumaticports 170 enable a negative pressure asserted through membrane gasket145 to pull surface 168 of blind pump wells 160 a and 160 b and surface168 of valve wells 164 together with sheeting 104 a of cassette 140. Theconfiguration makes wall 168 and sheeting 104 a operate as a singlemembrane for each of the individual pump chambers 112 and valve chambers114 of the disposable cassette.

Membrane gasket 145 also includes dead spaces 172, only which do notextend all of the way through plateau 158. Accordingly, dead spaces 172are only seen on the bulk surfaces 154 of FIG. 22. Dead spaces 172remove material from the membrane gasket where it is not needed and,accordingly, enable membrane gasket 145 to be made more costeffectively.

FIGS. 20 and 21 illustrate interface plate 185. Interface plate 185 canbe made of metal, such as aluminum, or plastic. Various configurationsfor interface plate 185 and cassette interface 180 are discussed belowin connection with FIGS. 23 to 30. Interface plate 185 includes asidewall 186, top wall 188 and an enclosed edge 202 extending from topwall 188. As discussed above, edge 202 fits frictionally within rim 156of membrane gasket 145 to help maintain a sealed environment between thetwo structures.

Pump chamber wells 190 a and 190 b are defined in or provided bymembrane plate 185. Pump wells 190 a and 190 b cooperate with pumpchambers 112 a and 112 b respectively of disposable cassette 140. Inparticular, pump wells 190 a and 190 b include pneumatic actuation ports198. When negative air pressure is supplied through ports 198, thenegative pressure pulls the combination of blind wall 168 and sheeting104 a associated with the pump chamber towards the wall of well 190 a or190 b. This expands the volume between sheet 104 a and pump chamber 112of rigid portion 110 of cassette 140 causing a negative pressure to beformed within the cassette, which in turn causes a volume of fluid(fresh or spent) to be pulled into the pump chamber 112. Likewise, whenpositive pressure is applied through aperture 198, the positive pressurepushes the combination of blind wall 168 and cassette sheeting 104 a atthe pump well 190/pump chamber 112 interface, pushing wall 168 andsheeting 104 a into or towards pump chamber 112 of rigid portion 110,which in turn dispels or pushes fluid from the respective pump chamber112 to the patient or drain.

Pump wells 190 a and 190 b each include a wall 192. Wall 192 fitssealingly and snugly within wall 162 of a respective blind well 160 a or160 b of membrane gasket 145. The sealed interface between walls 192 ofinterface plate 185 and walls 162 of pump wells 160 a and 160 b furtherenhances the sealed and separated operation of the various pumps andvalves within system 150.

Interface plate 185 also includes a plurality of raised valve seats 194.In particular, a valve seat 194 is provided for each blind valve well164 of membrane gasket 145. Each valve seat 194 and blind valve well 164corresponds to one of the valve chambers 114 of disposable cassette 140.Valve seats 194 include raised sidewalls 196 that extend outwardly fromtop surface 188 of interface plate 185. Valve wells 164 of membranegasket 145 fit snugly around valve seats 194, so that walls 166 of valvewalls 164 seal against walls 196 of valve seats 194.

Valve actuation ports 198 are defined at least substantially at thecenter of seats 194. In an embodiment, the top surfaces of valve seats194 slope downwardly towards the actuation ports 198. This enablesmating blind surface 168 and cassette sheeting 104 a to be pulled awayfrom valve chambers 114 of cassette 140 to open a respective valve toallow fluid to flow therethrough.

As seen in FIG. 16, each valve chamber 114 includes a relativelycentrally located protruding volcano-type port. When cassette 140 isused with system 150 the volcano ports each become aligned with one ofthe actuation ports 198. When positive pressure is applied through oneof the actuation ports 198, the positive pressure pushes the cooperatingblind wall 168 and cassette sheeting 104 a at the respective valve seat194 and valve chamber 114 of cassette 140, to cover or close the volcanoport, closing the respective valve chamber 114.

As seen best in FIG. 21, interface plate 185 includes a plurality ofgasket seal ports 200. A gasket seal port 200 is provided for each pumpwell 190 a and 190 b and for each valve seat 194. It should beappreciated from viewing FIGS. 21 and 22 that seal ports 200 mate withapertures 170 of membrane gasket 145. Seal ports 200 can extend part wayor all of the way through apertures 170. In an embodiment, apertures 170press-fit around ports 200 to create a sealed fit between ports and thewalls defining apertures 170.

Sealing membrane gasket 145 on the vertical surfaces 196 of theprotruding valve seats 194, walls 192 of pump wells 190 a and 190 b andvacuum ports 200 provide multiple seals for the pump areas and valveareas of the cassette interface. That is, besides the membrane gasketside seals, additional compression seals exist between interface plate185 and membrane gasket 145 as well as between gasket 145 and cassettesheeting 104 a.

In one embodiment the face of the membrane gasket 145 in the thinflexing sections facing the sheeting 104 a above the pump and valvechamber of cassette 140 is textured. The surface of that same side ofmembrane gasket 145 at the thicker sections that compress and sealagainst the cassette ribs of the pump chambers, valve chambers and flowpath separators of cassette 140 are not textured and have a fine, smoothsurface finish for creating a good seal between the cassette sheeting104 a and the gasket ridges 148 a, 148 b and 152.

The texturing of the thin sections of membrane gasket 145 provides flowchannels for the air from the vacuum ports to migrate across the face ofeach of the valve and pump chambers of cassette 140. The texturing alsotends to prevent membrane gasket 145 and cassette sheeting 104 a fromsticking together when it is time to remove the cassette from thesystem. It is also contemplated to introduce a small positive pressurethrough ports 200 at the end of the therapy to eject the cassette 140from the interface plate 185. Alternately, positive pressure can beapplied through valve actuation ports 198 (used to close the cassettevalve chambers 114 of cassette 140 when it is time to remove thecassette. This action bulges membrane gasket 145 above pump chambers 112and valve chambers 114 and push cassette 140 away from interface plate185.

In operation, negative pressure is applied through ports 200 andapertures 170 to pull cassette sheet 104 a tight against blind wall 168of membrane gasket 156 for a given pump chamber or valve chamber. Thisnegative pressure is applied throughout the treatment, regardless ofwhether a positive pressure or a negative pressure is being applied viathe actuation ports 198 of pump wells 190 a and 190 b and valve seats194.

As discussed above, the operation of applying positive and negativepressure to cassette 140 is computer-controlled. The processorcontrolling such actuation is also capable of receiving and processinginputs, such as pressure sensor inputs. For example, a pressure sensorcan be fitted and applied to sense the pressure within a manifoldlinking each of valve seal ports 200.

Using the pressure sensor, the processor in combination with a computerprogram can perform an integrity test having precision not previouslyavailable. Given the above described apparatus, if a hole develops ineither membrane gasket 145 or cassette sheeting 104 a, the vacuum levelin the manifold sensed by the sensor begins to degrade. The sensoroutput to the processor or logic implementor is indicative of thenegative pressure degradation. The processor and computer program detectthe decreasing signal and output that a leak is present. The output canprompt any of: (i) shutting down therapy, (ii) sounding an alarm, (iii)showing a visual message, and (iv) audibly describing that a leak ispresent to the patient or caregiver.

The processor also accepts one or more signal from any or more moisturesensor, such as a conductivity sensor. The one or more sensor is placedin the instrument below cassette 140, e.g., in a channeled well beneathcassette 140. The output of the conductivity sensor is combinedlogically with the output of the pressure sensor.

The logically combined signals from the pressure and conductivitysensors result in the following diagnostic ability. If a leak isdetected, e.g., negative pressure degradation is detected, but nomoisture is detected, the leak is logically determined to be frommembrane gasket 145. That is, cassette 140 is not leaking fluid into theconductivity sensor. If the leak is detected and fluid is detected, theleak is logically determined to be from cassette 140.

To the extent that it is feasible to use multiple pressure sensors withindividual pump walls 190 a and 190 b and valve seats 194 or tomultiplex one or more pressure sensors, the diagnostic ability of system150 can be expended to be able to pinpoint not only which component isleaking, but which area of which component is leaking. For example, thetubing running to ports 200 could be split between pump tubing and valvetubing. A first pressure sensor could multiplex between the tubingleading to the different pumps to pinpoint a leak in either the first orsecond pump. The conductivity sensor then tells the system if it is acassette pump leak or a gasket pump leak. A second pressure sensor couldmultiplex to look for leaks in the different valves. Valve one to valvefive for example might all check-out to be holding pressure, while valvesix shows a leak, meaning the portion of the cassette sheeting or gasketin operation with valve six is leaking. The conductivity sensor tellsthe system if it is the cassette sheeting or the gasket at the valve sixposition that is experiencing a leak.

Another advantage of the cassette interface of the present disclosure isillustrated via FIGS. 23, 24, 25A and 25B, 26A and 26B. System 10 in oneembodiment uses a Boyle's Law based fluid measurement method taught inU.S. Pat. No. 4,826,482 (“the '482 Patent”), the entire contents ofwhich are hereby incorporated by reference and relied upon. That methodoperates on the premise that the air being injected into (or evacuatedfrom) pump actuation port 198 is at the same temperature as the fluidflowing through cassette 140, and at the same temperature of the airwithin reference chambers 210 a and 210 b, which is heated to bodytemperature or about 37° C. If a temperature difference exists betweenthe dialysate and operating air temperatures, volumetric accuracy iscomprised.

It is difficult to quickly and accurately measure the temperature of airwhen the components mounting the temperature sensor are not at the sametemperature as the air that is being measured. Also at the present time,a minimum two-hour warm-up time is required before performing avolumetric calibration on the HomeChoice® Pro APD System, which requiresthat interface plate 185, reference chambers 210 a and 210 b, pumpchambers 112 in pumping cassette 110 and the fluid being pumped all bewarmed to about 37° C.

FIGS. 19 and 20 illustrate that pneumatic solenoid valves 202 aremounted directly to plate 182. FIG. 23 illustrates that volumetricreference chambers 210 a and 210 b, which hold a known volume of air,are located on the reverse side 204 of interface plate 185 in oneembodiment. The purposes and operation of volumetric reference chambers210 a and 210 b is discussed in the '482 Patent and in detail below inconnection with FIGS. 27, 28A to 28F and 29, which disclose animprovement over the '482 Patent method. It is enough now to understandthat chambers 210 a and 210 b are used to calculate a volume of fluidpumped through the cassette. The advantage here is that valves 202 andvolumetric reference chambers 210 a and 210 b are placed in closeproximity to each other and to the pneumatic pathways to membrane gasket145.

For reference, side 204 of interface plate 185 in FIG. 23 showsactuation ports 198 and gasket seal ports 200 as described above inconnection with FIGS. 20 and 21. In the illustrated embodiment,reference chambers 210 a and 210 b are blind wells formed in interfaceplate 185 with precision to have a fixed and known volume. In anembodiment, a controlled volume (weighed amount) of a highly thermallyconductive material such as cooper mesh is placed in volumetricreference chambers 210 a and 210 b, which tends to counter a coolingeffect created when high pressure air flows back from the pump chambersinto the low pressure reference chambers 210 a and 210 b. Air withinpressure reference chamber 210 a and 210 b quickly equilibrates to thetemperature of the copper mesh and the walls of the reference chambers.

In FIG. 23, interface plate 185 is formed from a thermally conductivematerial, such as metal, e.g., aluminum, copper, steel or stainlesssteel. In the present system, the thermally conductive interface plate185 is heated, e.g., by inductively producing a current that flowswithin interface plate 185, causing the plate to heat due to its bulkresistance. Alternatively a resistive heater is conductively coupled toplate 185, e.g., via heating strip 208.

Although not illustrated, a temperature sensing device, such as athermistor or thermocouple is attached to the manifold, e.g., nearreference chambers 210 a and 210 b. The temperature sensor sends asignal back to the processor or logic implementor, which controls apower supply supplying power to the resistive heater or the currentproviding device, such that the temperature of interface plate 185 ismaintained steady at a desired temperature. In one embodiment, interfaceplate 185 is heated to about 36° or 37° C.

Referring now to FIGS. 24, 25A, 25B, 26A and 26B, system 210 illustratesan alternative heated cassette interface embodiment that connects to aremotely located valve manifold, such as that used in the HomeChoice®Pro APD System. System 210 includes alternative interface plate 215 anda separate heated reference chamber module 220. FIG. 24 illustratesmodule 220 attached to alternative interface plate 215. FIGS. 25A and25B illustrate alternative interface plate 215 form the front and back,respectively. FIGS. 26A and 26B illustrate the reference chamber module220 from the front and back, respectively.

Alternative interface plate 215 in one embodiment is made of plastic,such as injection molded ABS, Delrin®, Noryl®, polycarbonate or anyother suitable plastic. A front surface 212 of plate 215 provides thecassette interface, which is shaped largely the same as the cassetteinterface of interface plate 185. Interface plate 215 includes aplurality of valve seats 214, which each include a raised plateau 216.Plateaus 216 each form a downwardly angled or conical inset 218, whichdefines an actuation port 222. In the illustrated embodiment, gasketseal ports 200 are not illustrated. It should be appreciated howeverthat gasket seal ports 200 could be added and that the membrane gasket145 shown above can be employed with alternative interface plate 215.

Alternative interface plate 215 includes alternative pump wells 230 aand 230 b, which each include a plurality of actuation ports 232 and aconductive metal, e.g., aluminum or cooper, interface 234. Interfaces234 are shown in the rear view of plate 215 in FIG. 25B as extendingthrough an aperture 236 in the back of pump wells 230 a and 230 b. Theconductive interfaces 234 contact the heated reference chambers ofheated reference chamber module 220, such that heat from the heatedreference chambers in turn heats conductive interfaces 234. Heatedconductive interfaces 234 in turn heat air present between pump wells230 a and 230 b and the mated membrane gasket.

FIGS. 24 and 25B show pneumatic fittings 238, which in one embodimentare connected to a remotely located valve manifold and to the moldedplastic interface plate 215. Because fittings 238 direct positive andnegative air flowing to the valve seats 214 (FIG. 25A) or 194 (FIG. 21)and to the valve wells 164 of membrane gasket 145, the temperature ofthis air is not relevant to volumetric pumping accuracy. That is, onlythe air flowing to the pump chambers 112 of cassette 140 needs to beheated. Accordingly, module 220 can be made in a relatively smallpackage, which fits onto interface 215.

FIGS. 26A and 26B illustrate heated volumetric reference chamber module220. As seen in FIG. 26A, volumetric reference chambers 240 a and 240 bare fitted into a casing 242 having a sidewall 244, a mounting plate 246and a cover 248. Sidewall 244, mounting plate 246 and cover 248 can bemade of metal or a thermally conductive plastic. Volumetric referencechambers 240 a and 240 b can be formed integrally as part of mountingplate 246 or be separate items attached to the mounting plate. Heatingwires 250 run to a cartridge style heating element, such as those madeby Watlow Electric Manufacturing Company (St. Louis, Mo.), ChromaloxCorporation (Pittsburgh, Pa.) or Tempco Electric Heater Corporation(Wood Dale, Ill.) and fit into an, e.g., round, mounting aperture.Heating wires 250 can also run to resistive heating elements that canfor example coil around or otherwise contact volumetric referencechambers 240 a and 240 b so as to heat the volumetric reference chambersconductively, convectively or via radiant energy. Again, a temperaturesensor is incorporated into heated module 220, so as to provide feedbackto a heating controller, which maintains the volumetric referencechambers at a steady and desired temperature, such as 36° or 37° C., oralternatively at an equilibrium or average operating temperature thatthe corresponding disposable cassette reaches when pumping dialysisfluid.

Volumetric reference chambers 240 a and 240 b each include a conductiveinterface 252, which mate with conductive interfaces 234 of pump wells230 a and 230 b shown in FIGS. 25A and 25B. Conductive interfaces 252are made of a thermally conducting material, such as copper or aluminum.Thus, it should be appreciated that heat from the heating elements istransferred to the reference chambers, which are also conductivealuminum or copper in one embodiment. Heat conducts to conductiveinterface 252, to conductive interfaces 234 and to the activation air,which is pumped back and forth from reference chambers 240 a and 240 bvia valves 254, through actuation ports 232 of pump wells 230 a and 230b of interface plate 215 to the membrane and gasket.

Although not shown, a suitable insulating material, can be dispersedaround conductive reference chambers 240 a and 240 b and housing 242 ofmodule 220. The insulating material can be insulating wool orfiberglass, for example. The insulative material can also be applied tothe tubing running from fittings 254 to the remotely located valvemanifold and back to the pump ports 232 over the relatively short tubingpathway to further minimize heat loss to the atmosphere. The closeproximity of the pneumatic components also lends the configuration tobeing heated, which enables the components to be kept at a desired,stable temperature. These features reduce temperature related errors inmeasuring volume of fluid pumped using both the method of the '482Patent and the improved method discussed below. The remotely locatedvalve manifold can also be heated to further improve volumetricaccuracy. The embodiments shown in FIGS. 24 to 26 are more complex thanthe embodiments of FIGS. 19 to 23; however, the latter embodiments movethe valves away from the cassette interface and allow the valves to beincased within a sound enclosure.

Real Time Volume Measurement

Referring now to FIG. 27, system 250 illustrates one embodiment for apneumatic control of dialysis system 10 described herein. The top ofsystem 250 represents the components described above in connection withFIGS. 19 to 24, 25A, 25B, 26A and 26B. LP, LS, LH, LF, LD, RP, RS, RH,RF, RD represent the valve wells of the membrane gasket and the valvechambers of the disposable cassette. Although ten valves are describedhere and in FIGS. 19 to 24, 25A, 25B, 26A and 26B, more or less valvesmay be provided based on many factors, such as supply bag capability,whether or not admixing is supported and whether inline or batch heatingis used.

The valving and pneumatic lines for gasket seal ports 200 are not shownin FIG. 27. As described above, ports 200 can be pressurized togethersuch that one or a couple of valves in combination with a manifoldrunning to each of ports 200 can control all the gasket seal ports 200.

Left and right pump chambers represent the pump wells of the manifoldand pump chambers 112 of the disposable cassette. VSL and VSR are thevolumetric reference chambers discussed above. As illustrated, pressuretransducer X-VSL monitors the pressure in reference chamber VSL.Pressure transducer X-VSR monitors the pressure in reference chamberVSR.

Valves C0 to C4 and D1 to D5 are three way valves 238 shown in FIGS. 24and 25B. Valves A0 and B4 are pump control valves 254 shown in FIG. 26A.The remainder of valves A, C and D are located elsewhere in instrument20.

System 250 also includes a plurality of positive and negative pressuretanks, NEG T (negative pressure, communicates with chambers VSL andVSR), POS T (positive pressure, communicates with chambers VSL and VSR),NEG P-L (negative pressure, communicates with left pump chamber), NEGP-R (negative pressure, communicates with right pump chamber), POS P-L(positive pressure, communicates with left pump chamber), and POS P-R(positive pressure, communicates with right pump chamber). Separatepressure transducers X-NEG T, X-POS T, X-NEG P-L, X-NEG P-R, X-POS P-L,X-POS P-R monitor the pressure in the respective pressure tanks.

The separate pressure and vacuum reservoirs NEG P-L, NEG P-R, POS P-Land POS P-R allow a pressure (vacuum) decay to be measured as fluid ispushed from (pulled into) pumping chambers 112 as described in detailbelow.

For reference, piston bellows, which can be located in the door ofinstrument 20, pushes the cassette against the interface plate and anoccluder bellows which can unclamp all lines (fail closed) are shown.Both bellows and the occluder are actuated pneumatically in oneembodiment.

System 250 also includes a processor or logic implementer operating withcomputer memory having program code configured to perform the belowdescribed real time method. System 250 can be operated with the heatedmanifolds discussed above, making the assumption of constant temperaturea more correct assumption.

Referring now to FIGS. 28A to 28F, an improved method for measuring thevolume of fluid pumped via pneumatic actuation is illustrated. FIGS. 28Ato 28D illustrate by example how the volume of fluid moved is calculatedafter its has been moved. Valves shown blackened are closed, whilenon-shaded valves are open. The actions shown in FIGS. 28A and 28B occurduring the relatively short rest measurement periods just prior to apump-out stroke shown above in connection with FIGS. 18A to 18C. Theactions shown in FIGS. 28C and 28D occur during the short restmeasurement periods just after the pump-out strokes of FIGS. 18A to 18C.

The chamber is full of fluid in FIGS. 28A and 28B. In FIG. 28A, thevalve (or valves) between chamber POS T and the pump chamber (e.g., leftpump chamber) is (are) open. The valve (or valves) between chamber POS Tand the associated volumetric reference chamber (e.g., VSL) is (are)closed. This allows the pump chamber to become pressurized to thepressure of POS T, e.g., 7 psig. A vent valve (e.g., A1 in FIG. 27) isopened such that the pressure in the volumetric reference chamber (e.g.,VSL) is zero. Volumetric reference chamber (e.g., VSL) has a knownvolume of 16.5 milliliters in the illustrated embodiment.

In FIG. 28B, the valve state switches such that valve (or valves)between chamber POS T and the pump chamber (e.g., left pump chamber) is(are) closed. The valve (or valves) between chamber POS T and theassociated volumetric reference chamber (e.g., VSL) is (are) opened.Vent valve (e.g., A1) is closed. This allows the pump chamber topressurize the volumetric reference chamber (e.g., VSL) to 2.4 psig,causing the pump pressure to drop from 7 psig to 2.4 psig.

The processor is configured to calculate the volume of air or gas V gasbehind the fluid pump chamber when full as follows:

V _(gas, full)=(P _(ref, final) −P _(ref, initial))/(P_(pressl, initial) −P _(pressl, final))*V _(ref),

wherein

P_(ref,final) is a final pressure in the volumetric reference chamber(e.g., VSL) after the medical fluid pump is allowed to pressurize thevolumetric reference chamber (e.g., VSL), 2.4 psig in the example;

P_(ref,initial) is the initial pressure in the reference chamber beforethe medical fluid pump is allowed to pressurize the volumetric referencechamber (e.g., VSL), zero psig in the example;

P_(pump, initial) is an initial pressure in the pressure chamber beforethe medical fluid pump is allowed to pressurize the volumetric referencechamber (e.g., VSL), here 7 psig. P_(pressl, final) is a final pressurein the pressure chamber after the medical fluid pump is allowed topressurize the volumetric reference chamber (e.g., VSL), here 2.4 psig;and

V_(ref) is the volume of the reference chamber, here 16.5 milliliters.

Thus V_(gas, full)=(2.4−0)/(7−2.4)*16.5 milliliters=8.6 milliliters.

Next, the valve chambers 114 of the disposable cassette are changed suchthat positive pressure from one of the pump stroke tanks POS P-L and POSP-R (illustrated in FIGS. 28E and 28F) pushes fluid from the pumpchamber to the patient or drain. The pump-out stroke is performed incombination with the real time fluid volume measurement shown below inconnection with FIGS. 28E and 28F. This is described below with the realtime pressure decay method.

Next, as shown in FIG. 28C the chamber has already been emptied. Thevalve (or valves) between chamber X-POS T and the pump chamber (e.g.,left pump chamber) is (are) open. The valve (or valves) between chamberX-POS T and the associated volumetric reference chamber (e.g., VSL) is(are) closed. This allows the pump chamber to become pressurized to thepressure of X-POS T, e.g., 7 psig. A vent valve (e.g., A1 in FIG. 27) isopened such that the pressure in the volumetric reference chamber (e.g.,VSL) is zero. Volumetric reference chamber (e.g., VSL) has the knownvolume of 16.5 milliliters.

In FIG. 28D, the valve state switches such that valve (or valves)between chamber X-POS T and the pump chamber (e.g., left pump chamber)is (are) closed. The valve (or valves) between chamber X-POS T and theassociated volumetric reference chamber (e.g., VSL) is (are) opened.Vent valve (e.g., A1) is closed. This allows the pump chamber topressurize the volumetric reference chamber (e.g., VSL) to 4.2 psig,causing the pump pressure to drop from 7 psig to 4.2 psig.

The processor is configured to perform the same calculation as shownabove, this time to calculate the volume of air or gas V_(gas) behindthe fluid pump chamber when empty:

V _(gas, empty)=(4.2−0)/(7−4.2)*16.5 milliliters=24.75 milliliters.

The volume of pumped between the measurement periods of FIGS. 28B and28C is then: fluid moved V_(fluid)=empty chamber air volumeV_(gas, empty)=full chamber air volume V_(gas, full), which is 24.75milliliters−8.6 milliliters=16.15 milliliters.

Referring now to FIGS. 28E and 28F, the apparatus for performing a realtime calculation of fluid pumped is illustrated. Here, pressure decay inthe pressure tank driving the pump chamber during the pump-out stroke(POS P-L and POS P-R) is monitored in real time. The processorcalculates the volume pumped in real time according to the equation:

V _(fluid,t)=(P _(POS P, initial) /P _(POS P,t)−1) (V _(POS P) +V_(gas, full)),

wherein

P_(POS P, initial) is an initial pressure of the pressure tank POS P-Land POS P-R prior to the pump-out stroke;

P_(POS P,t) is a pressure of the second pressure chamber at a time tduring the pump-out stroke;

V_(POS P) is a known volume of the second pressure chamber; and

V_(gas, full) is the calculated volume of gas in the pump chamber whenfull made above in connection with FIGS. 28A and 28B.

The steps of FIGS. 28E and 28F are made between the before and aftercalculations above, that is, between the steps of FIGS. 28B and 28C. InFIG. 28E, at the beginning of the pump-out stroke, the valve (or valves)between chamber POS T and the pump chamber (e.g., left pump chamber) is(are) closed. The valve (or valves) between chamber POS T and theassociated volumetric reference chamber (e.g., VSL) is (are) closed.Vent valve (e.g., A1 in FIG. 27) is also closed. The volume of air inthe pump chamber V_(gas, full) is known to be 8.6 milliliters asdiscussed above in connection with FIG. 28B. The volume of fixed volumetank POS P-L or POS P-R is known, e.g., 500 milliliters. The initialpressure P_(POS P, initial) is known, e.g., 1.5 psig.

The valve (or valves) between chamber POS P-L or POS P-R is (are) openedbeginning the pump-out stroke. At this moment the pressure begins todecay. The processor is configured to sample the pressure readings(P_(POS P,t)) from pressure transducer X-POS P-L or X-POS P-R, forexample every twenty milliseconds. The processor also calculates thereal time amount of fluid pumped using the above equation and themeasurement of P_(POS P,t). FIG. 28F shows an end of the pump-out strokeand a corresponding end of the pressure decay.

FIG. 29 shows a chart of what the decay (P_(POS P,t)), and resultingfluid volume (milliliters) calculated according to the above equation,could look like over the pump-out stroke. For ease of illustration, onlya few data points are shown. The pressure begins at the time that thepump-out stroke begins. Here, P_(POS P,t)=P_(POS P, initial), such thatthe ratio of same is one, causing the first term in the equation and theresulting fluid volume pumped to be zero.

At the second pump stroke time in FIG. 29, P_(POS P,t) has dropped to16.1 psi (absolute), making the first term in the equation above equalto 0.0062, which when multiplied by the combined volume of tank POS P-Lor POS P-R (500 milliliters) and the initial volume of air in the pumpchamber (8.6 milliliters) yields an absolute volume pumped of(0.0062)*508.6=3.16 milliliters.

At the third pump stroke time in FIG. 29, P_(POS P,t) has dropped to16.00 psia, making the first term in the equation above equal to 0.0125,which when multiplied by the combined volume of tank POS P-L or POS P-R(500 milliliters) and the initial volume of air in the pump chamber (8.6milliliters) yields an absolute volume pumped of (0.0125)*508.6=6.35milliliters.

At the fourth pump stroke time in FIG. 29, P_(POS P,t) has dropped to15.90 psia, making the first term in the equation above equal to 0.0189,which when multiplied by the combined volume of tank POS P-L or POS P-R(500 milliliters) and the initial volume of air in the pump chamber (8.6milliliters) yields an absolute volume pumped of (0.0189)*508.6=9.59milliliters.

At the fifth pump stroke time in FIG. 29, P_(POS P,t) has dropped to15.80 psia, making the first term in the equation above equal to 0.0253,which when multiplied by the combined volume of tank POS P-L or POS P-R(500 milliliters) and the initial volume of air in the pump chamber (8.6milliliters) yields an absolute volume pumped of (0.0253)*508.6=12.87milliliters.

At the sixth and final pump stroke time in FIG. 29, which is alsoillustrated in FIG. 28F, P_(POS P,t) has dropped to 15.70 psia (1.0psig), making the first term in the equation above equal to 0.0318,which when multiplied by the combined volume of tank POS P-L or POS P-R(500 milliliters) and the initial volume of air in the pump chamber (8.6milliliters) yields an absolute volume pumped of (0.0318)*508.6=16.19milliliters.

The final absolute fluid volume moved or pumped via the real timealgorithm, 16.19 milliliters, is virtually the same as the volume offluid calculated via the before and after algorithm of FIGS. 28A to 28D,16.15 milliliters (0.25% difference). The real time method howeverenables mid-pump stroke volumes to be known. As described above andshown below, there are many uses for the intermediate volumes includingbut not limited to determining: (i) if a full pump stroke has occurred;(ii) if a line occlusion has occurred; (iii) if a leak has occurred; and(iv) if multiple concentrates have been mixed properly, for example.

As discussed above, the real time fluid volume calculation can be usedin combination with the before and after fluid volume calculation. Itshould be appreciated however that the real time fluid volumecalculation does not have to be used in combination with the before andafter fluid volume calculation. That is, after the determination ofV_(gas, full) in FIG. 28B, the system can perform the real timecalculation shown in FIGS. 28E, 28F and 29, without thereafter doing thepost stroke reference chamber pressurization and calculation. It istherefore expressly contemplated to not use the post stroke referencechamber pressurization and calculation, which would negate the need forthe post stroke fluid measurement periods shown for example inconnection with FIGS. 18A and 18B for both fill and empty strokes. Thepost stroke fluid measurement period can be eliminated for systems thathave any number of pump chambers, e.g., one, two or three pump chambers.

FIGS. 28A to 28F and 29 show a pump-out stroke and associated fluidvolume measurement. It should be appreciated that the above methodologyalso applies to a pump-in or fill stroke. Here, the same pump chamber(left or right) and reference chamber (VSL or VSR) are used. The maindifference is that negative pressure is used to flex the cassettesheeting, pulling fluid from a supply or a patient into the pumpchamber. Thus viewing FIG. 27, negative pressure tank NEG P-L or NEG P-Rreplaces the positive pressure tanks Pos P-L or Pos P-R in FIGS. 28E and28F. Negative pressure would be used for example in the fresh fluid anddrain fluid filling phases shown below in connection with FIGS. 30 and31 discussed next. The POS T tank remains as shown in FIGS. 28E and 28Fas it is used for fluid measurement after the fact (28A through 28D) andnot in the real time fluid measurement.

Referring now to FIG. 30, the real time method above is used inconnection with a filling method 300 for the filling of both pumpchambers (left and right) in a dialysis system that employs an onlinemixing of dextrose and bicarbonate concentrates to form a biocompatibledialysate for the patient, which is advantageous physiologically for thepatient. For ease of illustration, it is assumed that left pump chamber,reference chamber VSL and negative pumping tank NEG P-L control thedextrose pumping. Right pump chamber, reference chamber VSR and negativepumping tank NEG P-R control the bicarbonate pumping. POS T is used forboth pump chambers.

In step 302 a and 302 b, system 250 of FIG. 27 fills left pump chamberwith dextrose and right pump chamber with bicarbonate. Here, it isassumed that the volume of air or gas in the pump chamber prior to thefill has been determined per the method of FIGS. 28A and 28B.

In step 304 a and 304 b, the real time calculation of dextrose andbicarbonate using the method described above in connection with FIGS.28A to 28F is made. One purpose for doing the real time calculation isto determine flowrate. That is, the processor can be further configuredto calculate the difference between the instant volume and a previouslycalculated volume to determine a real time flowrate knowing the timebetween measurements. For example in FIG. 29, the volume deltas are:3.16 milliliters, 3.19 milliliters, 3.24 milliliters, 3.28 millilitersand 3.32 milliliters. Assuming the time between pressure readings orsample time to be the same between each sample, the above deltas showthe flowrate of fluid during the pump out stroke to be graduallyincreasing (instantaneous rate=volume delta/sample time). This may benormal due to the configuration of the pneumatic pumping system or ananomaly of the particular pump stroke.

The real time flowrate information can be used for many purposes. Oneuse is for control of the heater. Copending patent application entitled“Dialysis Fluid Heating Systems”, filed Jul. 5, 2007, patent applicationSer. No. 11/773,903, discloses a dialysis fluid heating controlalgorithm that uses flowrate feedback to control power to the fluidheating element. The flowrate information determined in connection withthe real time volume calculations of step 304 a and 304 b is one way toprovide the flowrate feedback to the referenced heating controlalgorithm.

In step 306 a and 306 b, the volume measurements of dextrose andbicarbonate using the before and after pump stroke method of FIGS. 28Ato 28D is performed. In step 308 a and 308 b, the final real time volumeis compared to the final before and after volume. If the differencebetween the two is outside of a particular amount (e.g., 1 milliliter),method 300 assumes that air is present in the associated pump chamber.The real time fluid flow measurement is essentially measuring themovement of the pumping chamber sheeting. The after the fact volumetriccalculation only equals the real time measurement when no air is presentwithin the pump chamber. If real time and after the fact measurementsdiffer, air can be assumed to be present. If air is present, method 300attempts to remove the air, which may require a couple of attempts.Method 300 tracks the number of attempts via a counter and eventuallycauses an alarm if air continues to be present.

A first step of the air purge subroutine is to determine if a counter isgreater than a maximum amount of air removal tries N that method 300 iswilling to make before determining that an alarm should be posted asseen in connection with step 310 a and 310 b. If counter is greater thanN (test could alternatively be whether the counter is equal to N), andthe allotted number of air removal procedures has been exceeded, method300 resets the counter in step 312 a and 312 b, and posts an alarm instep 314 a and 314 b, e.g., an “air in the system alarm”, which can beat least one of an audio alarm, visual alarm, audiovisual alarm, signalsent to a nurse, operator, pager or control center. The user can clearthe alarm and resume the therapy. The procedure beginning at step 302 aand 302 b is then repeated. The alarm may or may not reappear.

If counter is less than or equal to N (test could alternatively bewhether the counter is less than N), and the allotted number of airremoval procedures has not been exceeded, method 300 increases the countby one in step 316 a and 316 b and causes instrument 20 to perform an“air purge” procedure in step 318 a and 318 b, which can for exampleinvolve opening the drain line valve and “burping” the air out a port ofthe pump chamber and into the drain line. The procedure beginning atstep 302 a and 302 b is then repeated.

Returning to the real time volume versus the before and after volumecomparison of step 308 a and 308 b, if the difference between the two isinside of a particular range (e.g., 0 to 1 milliliter), method 300 nextdetermines whether the fill was a complete fill in step 320 a and 320 b.For example, if the volume defined between the cassette pump chambers112 and the pump wells of the interface plate when mated is 16.5milliliters, method 300 can look to see whether the total volumedelivered meets or exceed some amount close to the defined volume, e.g.,fifteen milliliters. To perform this step, method 300 can look to thereal time total volume, the before and after volume or both.

If not enough fluid has been drawn into the pump chamber, e.g., volumeis less than fifteen milliliters and the number of attempts has beenexceeded a maximum number of attempts (step 322 a or 322 b), method 300checks if a line kink or other fluid flow obstruction is present andattempts to unkink the line or otherwise remove the occlusion. To do soagain may take a couple of tries. Method 300 tracks the number ofocclusion removal tries in steps 324 a and 324 b. If no kink orocclusion is present, the fluid source can be determined to be empty.

A first step of the occlusion removal subroutine is to increment a countin step 324 a and 324 b. A next step is to determine if the count isgreater than a maximum amount of occlusion removal tries N that method300 is willing to make before determining that an alarm should beposted. If counter is greater than N (test could alternatively bewhether the counter is equal to N), and the allotted number of occlusionremoval procedures has been exceeded, method 300 posts a continuousalarm that the operator needs to correct before therapy can continue.

If counter is less than or equal to N (test could alternatively bewhether the counter is less than N), and the allotted number ofocclusion removal procedures has not been exceeded, method 300 causesinstrument 20 to perform an “occlusion removal” procedure in step 326 aand 326 b, which can for example involve pushing fluid back to itssource or bag in step 326 a and 326 b in an attempt to unkink the lineor bag port. A pushback is a push of a pump chamber of fluid backtowards the source solution bag that is not allowing the pump chamber tofill with fluid. The pushback will fail if fluid cannot flow back to thesource indicating that the source line is kinked or occluded. A realtime pressure decay, or lack thereof, can be used to monitor thepushback flow, or lack thereof.

If the pushback is not successful as determined in connection with step328 a and 328 b, system 300 determines that the source is occluded instep 330 a and 330 b. If the pushback is successful as determined inconnection with step 328 a and 328 b, the source is determined to beempty in step 332 a and 332 b. Once an occluded source or empty sourceis detected, system 300 can cause an audible or visual alarms to beposted. System 300 can cause the fill to resume automatically one or twotimes before posting a non-recoverable alarm that requires userintervention. The counter in step 322 a and 322 b keeps track of thenumber of times the pushback attempt is made.

In step 334 a and 334 b, left and right pump chambers empty theirrespective concentrates into a line that connects to the patient, whichis long enough for the concentrates to mix sufficiently before thedialysate is delivered to the patient. In steps 336 a and 336 b, method300 determines using the real time fluid volume method of FIGS. 28A to28F whether the total dextrose volume delivered has reached the targeteddextrose pump stroke volume delivered and whether the total bicarbonatevolume delivered has reached the targeted bicarbonate pump stroke volumedelivered, respectively.

If the targeted dextrose volume delivered has not been met in step 336a, fluid delivery continues and method 330 determines whether the “realtime” (dextrose-bicarb) volume difference is greater than ½ millilitersin step 338 a. If not, left pump chamber continues its emptying ofdextrose at step 334 a, causing the real time evaluation of step 336 ato be made again. If real time (dextrose-bicarb) volume difference isgreater than ½ milliliter in step 338 a, the left patient valve (LP inFIG. 27) is closed momentarily to prevent the left pump chamber fromproceeding too far ahead of the right pump stroke volume delivered instep 340 a. Once the volume delivered by the left and right pumpchambers is within ½ milliliter, the left pump chamber will resume itsemptying of dextrose in step 334 a, causing the real time evaluation ofstep 336 a to be made again. Delivery of fluid from the left pump willstop when the left pump chamber has emptied, such that the target pumpstroke volume has been delivered.

If the target bicarbonate volume delivered has not been met in step 336b, method 330 determines whether a real time (bicarbonate-dextrose)volume difference is greater than ½ milliliter in step 338 b. If not,right pump chamber continues to empty bicarbonate again in step 334 b,causing the real time evaluation of step 336 b to be made again. If realtime (bicarbonate-dextrose) volume difference is greater than ½milliliter in step 338 b, the right patient valve (RP in FIG. 27) isclosed momentarily to prevent the right pump chamber from proceeding toofar ahead of the left pump stroke volume in step 340 b. Once the volumedelivered by the left and right pump chambers is within ½ milliliter,right pump chamber resumes its emptying of bicarbonate in step 334 b,causing the real time evaluation of step 336 b to be made again.Delivery of fluid from the right pump will stop when the right pumpchamber has emptied, such that the target pump stroke volume has beendelivered.

Once the dextrose and bicarbonate target pump empty volumes are met insteps 336 a and 336 b, respectively, the processor measures the totalvolumes delivered using the before and after sequence of FIGS. 28A to28D for dextrose and bicarbonate in steps 342 a and 342 b, respectively.In step 344, the processor determines whether a cumulative measureddextrose-bicarbonate volume is less than a threshold difference, e.g.,one milliliter. The processor also determines whether a cumulativemeasured bicarbonate-dextrose volume is less than a threshold, e.g., onemilliliter. In essence, the processor is determining whether thecumulative delivered volumes of dextrose and bicarbonate are within 1milliliter.

If the cumulative delivered volumes when compared are outside of thethreshold range, the processor adjusts the volume for the next pumpstroke by calculating a correction factor in step 346. For example, ifthe normal target pump stroke volume is 15 milliliters, the system 300will actually deliver a volume of 15 minus the correction factor for thedextrose. If the cumulative dextrose delivered volume exceeds thecumulative delivered bicarbonate volume by 1.2 milliliters, thecorrection factor is 1.2 milliliters and the next target stroke volumefor dextrose is 15−1.2 milliliters=13.8 milliliters.

The correction factor is similar when bicarbonate delivered is greaterthan dextrose delivered by 1 milliliter or more. The correction factoris zero when the cumulative dextrose delivered is less than cumulativebicarbonate delivered.

After step 346, or if the cumulative pump empty volumes when comparedare inside of the threshold range, the processor determines whether thesum of the cumulative dextrose and bicarbonate pump empty volumes iswithin a range (e.g., one milliliter) of a prescribed or programmedtotal dextrose and bicarbonate fill volume in step 348. If the measuredtotal is within range of the prescribed total, fill phase is complete instep 350.

If the measured total is outside the range of the prescribed total, theprocessor determines whether the cumulative measured volume is less thanthe prescribed pump empty volume by more than the next scheduled set ofpump strokes, e.g., 30 milliliters, in step 352. If it is, another setof pump strokes is delivered and step 352 is reached again. Steps 354and 356 calculate the targeted fill volume for the next set of pumpstrokes. Step 356 calculates each targeted volume at 15 milliliters lessthe correction factors calculated in step 346. Step 354 calculates thefill volume to be ½ of the remaining volume (programmed fill—cumulativemeasured dextrose and bicarbonate). If the remaining volume is 20milliliters, and the correction factor for dextrose is 1.2 milliliters,the next stroke target volumes for the last set of pump strokes arecalculated to be, for example:

(20 milliliters+1.2 milliliters)/2−1.2=9.4 milliliters for dextrose

(20 milliliters+1.2 milliliters)/2−0=10.6 milliliters for bicarbonate

The target set of pump stroke volumes adds up to 20 milliliters whilecorrecting the cumulative volume of dextrose so that the cumulativedextrose volume equals the cumulative volume of bicarbonate.

Referring now to FIG. 31, the real time method above is illustrated inconnection with a draining method 400 for the filling of one of the pumpchambers (left or right) with effluent fluid from the patient. For easeof illustration, left pump chamber, reference chamber VSL and negativepumping tank NEG P-L are used in this example. Right pump chamber,reference chamber VSR and negative pumping tank NEG P-R would beperforming the same method simultaneously, but asynchronously so thatthe right pump chamber is filling with effluent when left pump system isemptying and vice versa.

Draining method 400 determines if the drain is flowing properly and ifair is present. In step 402, left pump chamber is filled with effluent.In step 404, the processor determines the real time effluent volume andflow for the fill in the manner described above. In step 406, ifflowrate is greater than a normal flow minimum rate threshold, e.g., 50milliliters/minute, method 400 determines whether the real time volumecalculation of effluent fill exceeds a minimum pump stroke volumethreshold, e.g., 12 milliliters, in step 408. If not, left pump chambercontinues to fill with effluent in step 402, forming a loop that cyclesuntil the real time volume calculation of effluent fill exceeds thethreshold in step 408.

When the real time volume calculation of effluent fill exceeds thethreshold in step 408, the measurement of the effluent fill volume usingthe before and after pump stroke method of FIGS. 28A to 28D is performedin step 410. If the real time fluid volume moved is greater than thebefore and after stroke method of FIGS. 28A to 28D, air may have beendrawn into the pump chamber when the chamber filled with fluid. Thebefore and after pump stroke method of 28A to 28D will not be able todistinguish a pump chamber that contains 13 milliliters of fluid and 2milliliters of air from a pump chamber that contains only 13 millilitersof fluid because the air will compress regardless of which side of theflexible sheeting it resides, resulting in the same volume calculation.However, the flexible sheeting will move more when it accepts 13milliliters of fluid and 2 milliliters of air than it would if it hadonly accepted 13 milliliters. The HomeChoice® System marketed byeventual assignee of the present disclosure attempts to complete thefill of the pump chamber using an alternate source if the pump chamberfill volume is more than 3 milliliters short of the full volume. If theHomeChoice® System cannot fill the pump chamber completely, air isassumed to be present. The contents of the pump chamber are then pumpedto drain to eliminate the air. The HomeChoice® System remedy accordinglywastes time and fluid. The pump air detection and discharge regimeoccurring after step 410 is discussed below as step 438 eliminates.

Returning to step 406, if flowrate calculated via the real timecalculation is less than the normal flow minimum rate threshold, e.g.,50 milliliters/minute, method 400 determines if the real time flowrateis greater than an intermediate or low flowrate threshold, e.g., 30milliliters/minute, in step 412. If the real time flowrate is greaterthan the intermediate threshold, method 400 determines if a time T1 atwhich the flowrate is between the intermediate and high-end thresholds(e.g., between 30 and 50 milliliters/minute) is less than a preset time,e.g., 5:00 minutes in step 414. If the flowrate has remained between theintermediate and high-end thresholds for longer than the preset time,method 400 assumes that the patient line may be partially occluded andwill attempt to clear the line pushing fresh dialysate toward thepatient. If the pushback is unsuccessful an alarm will be posted (step476). If the pushback is successful (determined via the volume using thebefore and after pump stroke method of FIGS. 28A to 28D in step 416) themethod either advances to fill (step 300) or posts a low drain volumealarm (step 482). This routine is discussed in detail below.

If the flowrate has remained between the intermediate and high-endthresholds for less than the preset time, method 400 determines whetherthe real time volume calculation of effluent fill exceeds a threshold,e.g., 12 milliliters, in step 418. If not, timer T1 beginning at zeroseconds is initiated in step 420 and left pump chamber continues to fillwith effluent in step 402, forming a loop that cycles until (i) Tireaches the preset time (e.g., five minutes) in step 414 or (ii) thereal time volume calculation of effluent fill exceeds the threshold(e.g., 12 milliliters) in step 418.

When the real time volume calculation of effluent fill exceeds thethreshold in step 418, the measurement of the effluent fill volume usingthe before and after pump stroke method of FIGS. 28A to 28D is performedin step 410. The pump air detection and discharge regime occurring afterstep 410 is discussed below at step 438.

Returning to step 412, if flowrate calculated via the real timecalculation is less than the intermediate threshold, e.g., 30milliliters/minute, method 400 determines if the real time flowrate isgreater than a low end no-flow flowrate threshold, e.g., 12milliliters/minute, in step 422. If the real time flowrate is greaterthan the low end threshold, method 400 determines if a time T2 at whichthe flowrate is between the low end and intermediate thresholds (e.g.,between 12 and 30 milliliters/minute) is less than a second preset time,e.g., 3:00 minutes in step 424. In the illustrated embodiment T2 is lessthan T1, meaning method 400 does not wait as long at the lower flowratebefore running the occlusion routine at step 416 because an occlusion ismore likely at the lower flowrate.

If the flowrate has remained between the low end and intermediatethresholds for longer than the second preset time, method 400 assumesthat the patient line may be partially occluded and attempts to clearthe line by pushing fresh dialysate towards the patient. If the pushbackis unsuccessful an alarm is posted at step 476. If the pushback issuccessful (determined by measuring the pump fill volume using thebefore and after pump stroke method of FIGS. 28A to 28D in step 416),the pump advances to fill (step 300) or posts a low drain volume alarm(step 482). This routine is discussed in detail below.

If the flowrate has remained between the low end and intermediatethresholds for less than the second preset time T2, method 400determines whether the real time volume calculation of effluent fillexceeds a threshold, e.g., 12 milliliters, in step 426. If not, timer T2beginning at zero seconds is initiated in step 428 and left pump chambercontinues to fill with effluent in step 402, forming a loop that cyclesuntil (i) T2 reaches the preset time (e.g., three minutes) in step 424or (ii) the real time volume calculation of effluent fill exceeds thethreshold (e.g., 12 milliliters) in step 426.

When the real time volume calculation of effluent fill exceeds thethreshold in step 426, the measurement of the effluent fill volume usingthe before and after pump stroke method of FIGS. 28A to 28D is performedin step 410. The pump air detection and discharge regime occurring afterstep 410 is discussed below at step 438.

Returning to step 422, if flowrate calculated via the real timecalculation is less than the low end no-flow threshold, e.g., 12milliliters/minute, method 400 initiates a third timer T3 if the timerhas not yet been initiated in step 430. If the real time flowrate isless than the low end threshold, method 400 determines if a time T3 atwhich the flowrate is less than the low end threshold is less than athird preset time, e.g., 1:00 minute in step 432. In the illustratedembodiment T3 is less than T2, meaning method 400 does not wait as longat the low end flowrate before running the occlusion routine at step 416because an occlusion or an empty patient is more likely at the lowerflowrate.

If the flowrate has remained under the low end threshold for less thanthe second preset time T3, method 400 determines whether the real timevolume calculation of effluent fill exceeds a threshold, e.g., 12milliliters, in step 434. If not, and timer T3 is not equal to zeroseconds, method 400 causes left pump chamber to reduce suction pressurein step 436 (e.g., by changing NEG P-L from −1.5 psig to −1.2 psig asindicated in the pneumatic system 250 of FIG. 27).

At step 436 the patient is likely close to being empty or fully drained.To reduce discomfort in pulling the remaining effluent out of thepatient, method 400 lowers the suction pressure in step 436. Left pumpchamber continues to fill with effluent in step 402, forming a loop thatcycles until (i) T3 reaches the preset time (e.g., one minute) in step432 or (ii) the real time volume calculation of effluent fill exceedsthe threshold (e.g., 12 milliliters) in step 434.

When the real time volume calculation of effluent fill exceeds thethreshold in any of steps 408, 418, 426 or 434, the measurement of theeffluent fill volume using the before and after pump stroke method ofFIGS. 28A to 28D is performed in step 410 and a pump air detection checkis performed. Here, method 400 calculates the difference between thereal time calculation of effluent removed from the patient via themethod of FIGS. 28A to 28F and the volume calculated using the beforeand after pump stroke method of FIGS. 28A to 28D. If the volumedifference is less than a threshold difference (e.g., 1 milliliter) instep 438, the system assumes that little or no air is present and thatnormal pumping can continue because any air that may be present will notpass through the pump.

If the difference determined in step 438 is greater than the threshold,method 400 initiates a fourth timer T4 in step 440 if the timer has notyet been initiated. If the difference has remained out of range forgreater than a fourth preset time (e.g., three minutes) as determined instep 442, method 400 posts an air in the system alarm in step 444. If(i) the difference has not remained out of range for greater than thefourth preset time as determined in step 442 or (ii) the differencebetween the real time and before/after volumes is less than thethreshold, method 400 causes left pump chamber to empty the effluent todrain in step 446. However, if T4 is greater than three minutes, thesystem assumes that the pump chamber has been ingesting air from thepatient for three minutes and posts an alarm at step 444.

Step 448 creates a loop in which left pump chamber continues to empty todrain as long as the drain flow is greater than a threshold value, e.g.,80 milliliters/minute. When drain flow falls below the threshold, method400 determines if the real time volume calculation of effluent sent todrain exceeds a threshold volume, e.g., 12 milliliters, in step 450. Ifnot, method 400 determines if drain flow has fallen below a low endthreshold, e.g., 12 milliliters/minute, in step 452.

If drain flow has not fallen below the low end threshold in step 452, alonger timer T5 is initiated if not initiated already in step 454. Aloop is created as long as real time volume is less than the threshold,e.g., 12 milliliters, and drain flow remains above the low endthreshold, e.g., 12 milliliters/minute and below the upper threshold,e.g., 80 milliliters/minute until timer T5 reaches a fifth (longer)preset time (e.g., three minutes) in step 456, at which time method 400sends an alarm (audio, visual or audiovisual) to check the drain linefor an occlusion in step 458.

If drain flow has fallen below the low end threshold in step 452, ashorter timer T6 is initiated if not initiated already in step 460.Another loop is created as long as real time volume is less than thethreshold, e.g., 12 milliliters, and drain flow remains below the lowend threshold, e.g., 12 milliliters/minute, until timer T6 reaches asixth (shorter) preset time (e.g., thirty seconds) in step 462, at whichtime method 400 sends the alarm to check the drain line for an occlusionin step 458.

When drain flow falls below the threshold in step 448 and the real timevolume calculation of effluent sent to drain exceeds a threshold volume,e.g., 12 milliliters, in step 450, method 400 calculates the totaleffluent volume sent to drain via the before and after method of FIGS.28A to 28D as seen in step 464, after which left pump chamber beginsanother fill of effluent at step 402.

When any of the timers T1, T2 or T3 times out in steps 414, 424 or 432,respectively, it is possible that the patient line has an occlusion,which could for example be due to fibrin blockage or a partially kinkedline. At step 416, method 400 calculates the total effluent pulled fromthe patient during the current pump stroke using the before and aftermethod of FIGS. 28A to 28D. In step 466, left pump chamber empties theeffluent to drain. In step 468, the total effluent volume sent to drainvia the before and after method of FIGS. 28A to 28D is calculated, afterwhich left pump chamber pulls a bolus of fresh fluid from a supply bagin step 470.

Left pump chamber pushes the fresh bolus to the patient via the patientline to verify that fill can be performed and to remove any fibrinblockage or to unkink the patient line if it is partially occluded dueto a kink in step 472. If the pushback procedure is not successful,e.g., fluid cannot reach the patient or real time flowrate is below athreshold, as determined in step 474, method 400 in step 476 posts apatient line occluded alarm via any of the ways discussed above. If theprocedure is successful, e.g., fluid reaches the patient and/or realtime flowrate is above a threshold, as determined in step 474, method400 assumes that the patient is empty at step 478.

After the patient is determined to be empty in step 478, a total volumeof effluent pulled from the patient is calculated and compared to aminimum drain volume in step 480. If total effluent volume is less thana minimum volume, a low drain alarm is posted in step 482 via any of thetechniques described above. If total effluent volume reaches or exceedsthe minimum volume, system 10 employing method 400 advances to the fillphase 300 described above in connection with FIG. 30. The minimum volumecan be a percentage of the programmed fill volume when draining toempty. When draining to a target volume, for example with a tidaltherapy, the minimum volume is the target volume. Method 400 alsomonitors the cumulative volume of effluent drained after step 410. Thiscumulative volume is reported as the volume drained when a tidal drainends while under a normal flow condition. Otherwise, the cumulativedrain volume from step 480 is reported as the volume drained.

Temperature Sensor

Referring now to FIGS. 32 and 33, system 500 illustrates one possiblefluid temperature measuring apparatus and method for system 10.Temperature measuring system 500 is advantageous because it isnon-invasive. System 500 measures the temperature of fluid flowingthrough a portion of disposable set 50. For example, system 500 couldmeasure the temperature of fluid flowing through disposable cassette 28,100, 130, 140, e.g., upstream, downstream or directly at a fluid heatingpathway of a cassette used with inline heating. Or, the fluid could besensed while flowing through one of the fluid lines, such as directlyupstream and/or downstream of the fluid heater. Further alternatively,the fluid could be sensed while residing within a bag or container, suchas a warmer bag used with batch heating.

In the illustrated embodiment, system 500 includes a housing 502, whichis part of instrument 20 of system 10. For example, housing 502 can beintegrated into interface plate 185 described above in connection withFIGS. 19 to 21. When cassette 28, 100, 130, 140 is loaded intoinstrument 20, a portion of the cassette is pressed against housing 502.Housing 502 can be plastic or metal and should be at least substantiallyopaque, e.g., to infrared wavelengths. With the cassette 28, 100, 130,140 compressed against housing 502 and the door of instrument or machine20 closed on the other side of cassette 28, 100, 130, 140, littleambient light reaches the portion of cassette 28, 100, 130, 140interfacing with system 500.

Sheeting 102 of cassette 28, 100, 130, 140 includes a portion 504transparent, e.g., to infrared wavelengths and a non-transparent oropaque portion 506. Portions 504 and 506 are placed adjacent to housing502. Opaque portion 506 is formed for example via an inking (e.g.,ink-jetting), printing or painting (e.g., spray painting) process.Alternatively, opaque portion 506 is formed via an opaque patch adheredto the disposable item. The size of opaque portion 506 can range fromabout ¼ inch by ¼ inch (6.4 mm by 6.4 mm) to about one inch by one inch(2.54 cm by 2.54 cm) or the same size in diameter if circular.Transparent portion 504 can be the clear sheeting 102 and can have aninfrared target area at least as large as that of opaque portion 506.The size of the target area depends upon the infrared sensor selectedand the distance that the sensor is mounted away from the target area.For example, a MIKRON M50 infrared sensor suitable for this applicationhas a ½ inch (1.27 mm) target diameter when pressed against the target.The target diameter increases to 1¼ inch (3.18 cm) when the sensor ismoved to six inches (15.25 cm) from the target.

Temperature measuring system 500 includes an arm 508, which holds atemperature sensor 510. Arm 508 is able to pivot back and forth at apivot point 512, so that temperature sensor 510 is pointed selectivelyat either transparent portion 504 or opaque portion 506. Temperaturesensor 510 in one embodiment is an infrared temperature sensor. Suitableinfrared temperature sensors 510 are provided by PerkinElmer (Walthen,Mass.), Dexter Research (Dexter, Mich.), Electro Optical Components(Santa Rosa, Calif.).

In the illustrated embodiment, housing 502 includes electromagnets 514.When energized the electromagnets will push and/or pull on the metalportion of magnetized pivot arm 516. Reversing the polarity will causethe polarity orientation to change. Arm 508 includes a magnetic, e.g.,steel, portion 516, which is pulled towards one of the electromagnets514 when that electromagnet is energized. Electromagnets control theorientation of the infrared temperature sensor so that infraredtemperature sensor 510 can be pointed selectively (i) at opaque portion506 to take a first temperature reading, temp wall, of the sheeting 102only as seen in FIG. 32 or (ii) at clear portion 504 to take a secondtemperature reading, temp wall and fluid, which is a combination(A*temp_(wall)+B*temp_(fluid)) of the sheeting 102 and the fluid withinthe sheeting 102 as seen in FIG. 33. A and B are constants dependentupon the film or tube thickness and composition and are determinedexperimentally.

Because temp_(wall) is measured and known, the fluid temperaturetemp_(fluid) can be calculated using measured temp_(wall) and measuredtemp_(wall and fluid) according to the equation:

${temp}_{fluid} = \frac{\begin{bmatrix}{{{measured}\mspace{14mu} {temp}_{{wall}\mspace{14mu} {and}\mspace{14mu} {fluid}}} -} \\{(A)*( {{measured}\mspace{14mu} {temp}_{wall}} )}\end{bmatrix}}{B}$

A processor and memory on a temperature controller or at a centralprocessing unit store constants A and B and perform the abovecalculation. Temperature sensing system 500 should provide near realtime, non-invasive monitoring of the fluid temperature.

Sensor 510 is flipped back and forth and the different temperaturemeasurements are taken for example, every second. Alternatively, twoindependent infrared temperature sensors are used, one for infraredenergy transmissive portion 504 and the other for infrared energynon-transmissive portion 506. Further, alternatively, a dual orquadruple infrared sensor package is used, such as a Perkinselmer® TPS2534 dual element thermopile or TPS-4339 Quad Element thermopile. Thequad element system provides redundant temperature measurement. Multiplesensors remove calibration complexity.

A motor or solenoid could be used instead of electromagnets. Furtheralternatively, arm 508 could be pushed by a spring to one pivot positionand pneumatically retracted to the second pivot position.

Referring now to FIG. 34, data illustrating the accuracy of fluidsensing system 500 is shown. System 500 in FIG. 34 appears to providetemperature readings non-invasively that approach the accuracy andresponse time of an invasive temperature sensor. The correlation betweenthe readings from a resistance temperature detector (“RTD”) sensorimmersed in the fluid to the calculated readings from infrared sensingsystem 500 is good especially considering that the fluid temperaturerose from just over 20° C. to over 50° C. during a ten minute time spanin which the temperature readings were taken. In the example, constant Awas set to 0.877985 and constant B was set to 0.109635. The curve fitline was found to be T_(CALC)=1.047*T_(RTD)−0.0303.

Multi-Chamber Bag Open Sensor

Referring now to FIGS. 35 and 36, inductive sensing system 530illustrates one embodiment for detecting: (i) whether a single chambersupply bag 40 (referring generally to supply bags 40 a to 40 d discussedabove) or a multi-chamber supply bag 540 is residing on a particular oneof shelves 32, 34, 36 and 38; and (ii) if the supply bag is amulti-chamber supply bag 540, whether an associated frangible seal 542has been broken allowing two or more concentrates 544 a and 544 b fromseparate chambers 546 a and 546 b, respectively, to mix.

Multi-chamber supply bag inductive sensing system 530 measures current,which for a filly opened container is indicative of either electricalconductivity or electrical impedance. The measured current indicateswhether frangible seal 542 between chambers 546 a and 546 b ofmulti-chamber bag 540 has been broken so that previously separatedsolutions can mix prior to delivery to a patient.

The different concentrates 544 a and 544 b within separate chambers 546a and 546 b of multi-chamber bag 540 have different concentrations ofions. The different ionic nature of different concentrates 544 a and 544b provides an opportunity to correlate a measured current in a mixedsolution to a conductivity or impedance of the solution. System 530 canthereby compare the determined conductivity or impedance with anexpected conductivity or impedance to confirm whether the concentrateshave been mixed properly. System 530 is non-invasive, which isadvantageous when dealing with sterile medical fluids, such as dialysisfluids. It should be appreciated that system 530 can also operate withnon-sterile or non-injectable fluids.

System 530 includes a first coil 532 and a second coil 534, which arelocated in different positions within the limits of the tray or shelf(e.g., one of shelves 32 to 38) onto which multi-chamber bag orcontainer 540 is placed for treatment. For example, coils 532 and 534are installed on top of or underneath the tray or shelf (e.g., one ofshelves 32 to 38) or are laminated within the tray or shelf. Ifinstalled on top of the tray, coils 532 and 534 can be covered with aprotective coating or layer. Coils 532 and 534 can for example be formedfrom single stranded wire or multi-stranded wire, such as litzwire. Inthe illustrated embodiment, coils 532 and 534 are pancake or flat coils.

One of coils 532 and 534 performs a transmitter function while the otherof the coils performs a receiver function. The coils can be dedicated toone of the functions, e.g., coil 532 transmits and coil 534 receives asshown in FIGS. 36 and 37. Alternatively, coils 532 and 534 alternatebetween the transmitter and receiver functions.

A signal (voltage or current) generator 536 excites transmitter coil 532with a signal that varies with time, such as sine wave, square wave,sawtooth wave or other time variable wave. Generator 536 can be forexample (i) a logic level oscillator, (ii) a combination of oscillatorand filter or (iii) a waveform generator circuit. One suitable voltagerange includes four to twenty volts. Transmitter coil 532 induces smallcurrents in the dialysate, while receiver coil 534 senses thosecurrents. The intensity of the currents that receiver coil 534 sensesdepends on the type of solution and the degree of electrical couplingbetween bags and coils 532 and 534. For example, if the shape of thesupply bag or container is such that its footprint does not project ontop of a receiver coil, the receiver coil will not sense any current. Ifthe shape of the supply bag or container is such that its footprint doesnot project on top of a transmitter coil, the transmitter coil willinduce no current or relatively little current into the solution.

FIG. 35 shows that unopened seal 542 causes container 540 to couple lesseffectively with the flat areas of chambers 546 a and 546 b that lieflat on the tray or shelf. Accordingly, a sensor or measuring device 538will measure less current from receiver coil 534. This level of currentin FIG. 35 is shown to reside in a “not mixed” range. Current measuringdevice 538 in one embodiment is a multimeter or an ammeter.

FIG. 36 shows that opened seal 542 couples equally effectively with theflat areas of chambers 546 a and 546 b, since the entire bag orcontainer now lies flat on the tray or shelf. Accordingly, sensor ormeasuring device 538 measures more current from receiver coil 534. Thislevel of current in FIG. 36 is shown to reside in a “mixed” range.

FIGS. 37A to 37D illustrate an inductive system 560 that can determinewhether bag 540 is positioned and oriented correctly on tray or shelf32, 34, 36 or 38. Bag 540 shown from the top in FIGS. 37A to 37D showsfrangible seal 542 separating chambers 546 a and 546 b. System 560includes four coils 532 a, 532 b, 534 a and 534 b. Each coil can be usedfor either transmission or reception. The arrows represent some of thepossible couplings between the coils.

FIG. 37A illustrates a proper loading of bag 540, in which a port orpigtail 548 of bag 540 is aligned with and rests in aperture 35 of trayor shelf 32, 34, 36 or 38. Here, seal 542 separates coils 532 a and 532b from coils 534 a and 534 b, respectively. Seal 542 does not separatecoil 532 a from coil 534 a or coil 534 a from coil 534 b. The properloading position or orientation of FIG. 37A therefore results in asignature inductive coupling pattern of (i) coil 532 a to coil 532b—high coupling, (ii) coil 534 a to coil 534 b—high coupling, (iii) coil532 a to coil 534 a—low coupling, and (iv) coil 532 b to coil 534 b—lowcoupling.

The improperly loaded bag 540 of FIG. 37B on the other hand results in adifferent inductive coupling pattern of (i) high coupling, (ii) highcoupling, (iii) high coupling, and (iv) high coupling because all fourcoupling coils are located on one side of frangible seal 542. Theimproperly loaded bag 540 of FIG. 37C results in still a differentinductive coupling pattern of (i) low coupling, (ii) low coupling, (iii)high coupling, and (iv) high coupling due the position of seal 542relative to the coils illustrated in FIG. 37C. The improperly loaded bag540 of FIG. 37D results in the same inductive coupling pattern of FIG.37C, namely, (i) low coupling, (ii) low coupling, (iii) high coupling,and (iv) high coupling due the position of seal 542 relative to thecoils illustrated in FIG. 37D.

A system controller takes the four measurements before seal 542 isbroken and categorizes the coupling signature into either a bag properlyloaded state or an improperly loaded state. The electronics of system 10in one embodiment include a multiplexer that sequences through each oftransmitter/receiver pairs (i) to (iv) upon receiving a signal from aload cell detecting that a bag has been loaded or upon receiving aninput from the user that a bag or bags have been loaded. A single signalsource 536 can be multiplexed to a desired coil functioning as thetransmitter for the particular pair being sensed, e.g., coil 532 a forpair (i), coil 534 a for pair (ii), coil 532 a for pair (iii), and coil534 a for pair (iv) shown above. The multiplexer also sequences througha plurality of electrical switch states to electrically connect theappropriate coils of each pair (i) to (iv) to source 536 and sensor 538at the appropriate time.

It is also possible, after determining that bag 540 has been loadedproperly, that the controller can verify from the inductive couplingsignature that the composition of concentrate solutions 544 a and 544 bin compartments 546 a and 546 b is correct according to an expectedconductivity for each solution. Tested pairs (iii) and (iv) for thecorrect bag position of FIG. 37A reveal the conductivity forconcentrates 544 a and 544 b of compartments 546 a and 546 b,respectively. If a conductivity is out of an expected range an error canbe generated. The controller can also verify the integrity of seal 542.Before allowing treatment to begin, system 560 also verifies that seal542 has been opened allowing concentrates 544 a and 544 b to mix. Oncethe solution is mixed, the conductivity of the mixed dialysate can alsobe checked.

Correct bag positioning is useful for systems that use gravity for anyof the treatment operations. Verification of each of the individualsolutions allows determining if concentrations are adequate for theintended treatment. Verification of the integrity of the seal allowsinstrument 12 to ascertain that the solutions have not been mixed beforetreatment has begun. Premature mixture of the solutions considerablyshortens the shelf life of the product. Such measurement ensures that nodegradation of the solution has occurred.

The above-mentioned controller can operate directly or indirectly with acentral processing unit, which in turn operates with a video controllerand graphical user interface (“GUI”). If all of the above checks areverified, system 10 causes GUI to display a “bag loading ok” or similarmessage and allows therapy to continue. If one of the bags 540 is loadedincorrectly, system 10 causes GUI to display a “check bag loading” orsimilar message and perhaps even identifies the bag, e.g., “checkloading of second bag from top”. If the bags 540 are loaded correctlybut system 560 detects an abnormal conductivity, system 10 causes GUI todisplay a “check solution of bags loaded” or similar message and perhapseven identifies the bag, e.g., “check solution in second bag from top”.If bag loading and concentration are verified but the user tries tobegin therapy without opening one or all of bags 54, system 10 causesthe GUI to display a “open bag seal prior to treatment” or similarmessage and perhaps even identifies the bag, e.g., “open seal of top bagprior to treatment”.

FIGS. 4 to 9 illustrate a bag management system 30, which holds multiplesupply bags at an angle for fluid flow and air handling purposes. Itshould be appreciated that inductive sensing systems 530 and 560 canoperate at the bag angle of system 30, alternatively with bags 540loaded at least substantially horizontally or further alternatively withbags 540 loaded at least substantially vertically. In slanted system 30,the coils can be laminated to an upper or lower surface of each tray orbe embedded in the tray. With a vertical manager, the coils can beconnected to one or more vertical bar that runs vertically up one of thebags and presses respective coils against each bag. Signals to the coilsare supplied through vertical support bars. The bag management systemscan supply additional information such as weight information via a loadcell.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present subjectmatter and without diminishing its intended advantages. It is thereforeintended that such changes and modifications be covered by the appendedclaims.

1. A medical fluid flow control system comprising: an interfaceincluding a first pump area, the first pump area of the interfaceincluding a pneumatic actuator port and a gasket seal port; and amembrane gasket including a second pump area for mating with the firstpump area, the second pump area including a blind section which coversthe pneumatic actuator port when the gasket is mated with the interface,the second pump area further including an aperture, the aperture sizedand positioned to seal around the gasket seal port, allowing a negativepressure to be applied through the gasket seal port to a flexible sheetof a pumping cassette.
 2. The medical fluid flow control system of claim1, further including the pumping cassette, the pumping cassette defininga pump chamber, a pumping portion of the flexible sheet covering thepump chamber.
 3. The medical flow control system of claim 2, which isconfigured to mate the pumping portion of the flexible sheet with theblind section of the second pump area, the blind section and the pumpingportion of the flexible sheet flexing together to pull dialysis fluid inand push dialysis fluid out of the pump chamber of the pumping cassette.4. The medical fluid flow control system of claim 2, the negativepressure applied through the gasket seal port sealing the pumpingportion of the flexible sheet to the second pump area.
 5. The medicalfluid flow control system of claim 2, wherein the pump chamber of thecassette has a shape at least substantially similar to a shape of thesecond pump area, which is at least substantially similar to a shape ofthe first pump area.
 6. The medical fluid flow control system of claim1, wherein the first pump area includes at least one of a well and araised ridge.
 7. The medical fluid flow control system of claim 6,wherein at least one of: (i) the pneumatic actuator port is a borethrough the well, (ii) the gasket seal port resides adjacent to thewell, and (iii) the blind section of the pump area of the gasket issized to seal around the raised ridge of the first pump area.
 8. Themedical fluid flow control system of claim 1, wherein the gasket sealport projects from a base of the interface so as to be able to extend atleast partially through the aperture in the membrane gasket.
 9. Themedical fluid flow control system of claim 1, which includes anadditional pump area of the interface, which mates with an additionalpump area of the gasket.
 10. The medical fluid flow control system ofclaim 1, which includes a pressure sensor monitoring the negativepressure, and a logic implementor operable with an output of thepressure sensor to determine if a leak associated with one of thefollowing has occurred (i) the second pump area and (ii) a portion ofthe flexible sheet of the pumping cassette mated with the second pumparea.
 11. The medical fluid flow control system of claim 10, whichincludes a fluid sensor, the logic implementor further configured todetermine (i) that the leak is in the membrane gasket if the fluidsensor does not detect a fluid or (ii) that the leak is in the flexiblesheet of the pumping cassette if the fluid sensor detects a fluid.
 12. Amedical fluid flow control system comprising: an interface including afirst valve area, the first valve area including a pneumatic actuatorport and a gasket seal port; and a membrane gasket including a secondvalve area for mating with the first valve area, the second valve areaincluding a blind section which covers the pneumatic actuator port whenthe gasket is mated with the interface, the second valve area furtherincluding an aperture, the aperture sized and positioned to seal aroundthe gasket seal port, allowing a negative pressure to be applied throughthe gasket seal port to a flexible sheet of a pumping cassette.
 13. Themedical fluid flow control system of claim 12, further including thepumping cassette, the pumping cassette defining a valve chamber, a valveportion of the flexible sheet covering the valve chamber.
 14. Themedical flow control system of claim 13, which is configured to mate thevalve portion of the flexible sheet with the blind section of the secondvalve area, the blind section and the valve portion of the flexiblesheet flexing together to open and close a fluid pathway of the pumpingcassette.
 15. The medical fluid flow control system of claim 13, thenegative pressure applied through the gasket seal port sealing the valveportion of the flexible sheet to the second valve area.
 16. The medicalfluid flow control system of claim 13, wherein the valve chamber of thecassette has a shape at least substantially similar to a shape of thesecond valve area, which is at least substantially similar to a shape ofthe first valve area.
 17. The medical fluid flow control system of claim12, wherein the first valve area includes a raised seat, the pneumaticactuator port being a bore through the raised seat.
 18. The medicalfluid flow control system of claim 17, wherein the gasket seal portresides adjacent to the raised seat.
 19. The medical fluid flow controlsystem of claim 17, wherein the blind section of the second valve areais sized to seal around the raised seat of the first valve area.
 20. Themedical fluid flow control system of claim 12, which includes anadditional valve area of the interface, which mates with an additionalvalve area of the gasket.
 21. The medical fluid flow control system ofclaim 12, which includes a pressure sensor monitoring the negativepressure, and a logic implementor operable with an output of thepressure sensor to determine if a leak associated with one of thefollowing has occurred (i) the second valve area and (ii) a portion ofthe flexible sheet of the pumping cassette mated with the second valvearea.
 22. The medical fluid flow control system of claim 21, whichincludes a fluid sensor, the logic implementor further configured todetermine (i) that the leak is in the membrane gasket if the fluidsensor does not detect a fluid or (ii) that the leak is in the flexiblesheet of the pumping cassette if the fluid sensor detects a fluid.
 23. Amedical fluid flow control system comprising: an interface including apump actuator port, a pump seal port, a valve actuator port and a valveseal port; a membrane gasket including a pump actuation area, a pumpaperture, a valve actuation area and a valve aperture; a pumpingcassette, the cassette defining a pump chamber and a valve chamber, apump portion of a flexible sheet covering the valve chamber, and a valveportion of the flexible sheet covering the valve chamber; wherein thepump seal port and valve seal port are operable with the pump and valveapertures to seal (i) the pump portion of the flexible sheet to the pumpactuation area of the membrane gasket and (ii) the valve portion of theflexible sheet to the valve actuation area of the membrane gasket; andwherein the pump actuator port and valve actuator port are configured tomove (i) the pump portion of the flexible sheet and the pump actuationarea of the membrane gasket at the pump chamber of the cassette and (ii)the valve portion of the flexible sheet and the valve actuation area ofthe membrane gasket at the valve chamber of the cassette.
 24. Themedical fluid flow control system of claim 23, wherein at least one of(i) the pump actuation area of the membrane gasket includes a blindsection that covers the pump actuator port of the interface and (ii) thevalve actuation area of the membrane gasket includes a blind sectionwhich covers the valve actuator port of the interface.
 25. The medicalfluid flow control system of claim 23, which includes a pressure sensormonitoring a negative pressure, and a logic implementor operable with anoutput of the pressure sensor to determine if a leak associated with oneof the following has occurred (i) the pump actuation area of themembrane gasket and (ii) a portion of the flexible sheet of the pumpingcassette mated with the pump actuation area of the membrane gasket;(iii) the valve actuation area of the membrane gasket and (ii) a portionof the flexible sheet of the pumping cassette mated with the valveactuation area of the membrane gasket.